rs8058694

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001171.6(ABCC6):c.1896C>A(p.His632Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,608,938 control chromosomes in the GnomAD database, including 178,917 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14343 hom., cov: 31)

Exomes 𝑓: 0.47 ( 164574 hom. )

Consequence

ABCC6
NM_001171.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.15

Publications

45 publications found

Variant links:

Genes affected

ABCC6 (HGNC:57): (ATP binding cassette subfamily C member 6) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]

ABCC6 Gene-Disease associations (from GenCC):

arterial calcification, generalized, of infancy, 2
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
autosomal recessive inherited pseudoxanthoma elasticum
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), G2P
arterial calcification of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ABCC6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.1311641E-4).

BP6

Variant 16-16185006-G-T is Benign according to our data. Variant chr16-16185006-G-T is described in ClinVar as Benign. ClinVar VariationId is 433247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6 link	c.1896C>A	p.His632Gln	missense_variant	Exon 15 of 31	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ABCC6	ENST00000205557.12 link	c.1896C>A	p.His632Gln	missense_variant	Exon 15 of 31	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6 link	n.1896C>A		non_coding_transcript_exon_variant	Exon 15 of 29	2		ENSP00000405002.2
ABCC6	ENST00000622290.5 link	n.1896C>A		non_coding_transcript_exon_variant	Exon 15 of 32	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64716

AN:

151590

Hom.:

14342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.516

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.425

GnomAD2 exomes

AF:

0.419

AC:

105156

AN:

251100

AF XY:

0.413

show subpopulations

Gnomad AFR exome

AF:

0.350

Gnomad AMR exome

AF:

0.470

Gnomad ASJ exome

AF:

0.426

Gnomad EAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.490

Gnomad OTH exome

AF:

0.445

GnomAD4 exome

AF:

0.468

AC:

681571

AN:

1457230

Hom.:

164574

Cov.:

AF XY:

0.461

AC XY:

334447

AN XY:

725092

show subpopulations

African (AFR)

AF:

0.349

AC:

11668

AN:

33392

American (AMR)

AF:

0.468

AC:

20888

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

11175

AN:

26096

East Asian (EAS)

AF:

0.186

AC:

7390

AN:

39680

South Asian (SAS)

AF:

0.261

AC:

22472

AN:

86194

European-Finnish (FIN)

AF:

0.454

AC:

24237

AN:

53362

Middle Eastern (MID)

AF:

0.352

AC:

2028

AN:

5762

European-Non Finnish (NFE)

AF:

0.501

AC:

555403

AN:

1107822

Other (OTH)

AF:

0.437

AC:

26310

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

18961

37923

56884

75846

94807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15858

31716

47574

63432

79290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.427

AC:

64726

AN:

151708

Hom.:

14343

Cov.:

AF XY:

0.417

AC XY:

30888

AN XY:

74128

show subpopulations

African (AFR)

AF:

0.354

AC:

14637

AN:

41404

American (AMR)

AF:

0.443

AC:

6750

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

1472

AN:

3470

East Asian (EAS)

AF:

0.158

AC:

816

AN:

5160

South Asian (SAS)

AF:

0.249

AC:

1204

AN:

4828

European-Finnish (FIN)

AF:

0.437

AC:

4588

AN:

10506

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.499

AC:

33797

AN:

67792

Other (OTH)

AF:

0.419

AC:

883

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1895

3789

5684

7578

9473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

596

1192

1788

2384

2980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.462

Hom.:

55250

Bravo

AF:

0.428

TwinsUK

AF:

0.495

AC:

1836

ALSPAC

AF:

0.492

AC:

1895

ESP6500AA

AF:

0.358

AC:

1574

ESP6500EA

AF:

0.502

AC:

4313

ExAC

AF:

0.415

AC:

50419

Asia WGS

AF:

0.211

AC:

731

AN:

3478

EpiCase

AF:

0.483

EpiControl

AF:

0.479

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive inherited pseudoxanthoma elasticum

Benign:2

Mar 01, 2021

PXE International

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pseudoxanthoma elasticum, forme fruste

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Arterial calcification, generalized, of infancy, 2

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.051

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.097

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.27

T;T

MetaRNN

Benign

0.00021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.62

N;N

PhyloP100

-1.1

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.72

N;.

REVEL

Uncertain

0.29

Sift

Benign

0.24

T;.

Sift4G

Benign

0.65

T;T

Polyphen

0.0010

B;.

Vest4

0.026

MutPred

0.29

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MPC

0.067

ClinPred

1.0

GERP RS

-9.0

Varity_R

0.14

gMVP

0.24

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over