chr16-16198114-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001171.6(ABCC6):c.1245G>A(p.Val415Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,611,634 control chromosomes in the GnomAD database, including 87,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7118 hom., cov: 33)

Exomes 𝑓: 0.33 ( 80315 hom. )

Consequence

ABCC6
NM_001171.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.804

Publications

18 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 16-16198114-C-T is Benign according to our data. Variant chr16-16198114-C-T is described in ClinVar as Benign. ClinVar VariationId is 433228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.804 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6 link	c.1245G>A	p.Val415Val	synonymous_variant	Exon 10 of 31	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ABCC6	ENST00000205557.12 link	c.1245G>A	p.Val415Val	synonymous_variant	Exon 10 of 31	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000574094.6 link	c.1245G>A	p.Val415Val	synonymous_variant	Exon 10 of 11	5		ENSP00000507301.1
ABCC6	ENST00000456970.6 link	n.1245G>A		non_coding_transcript_exon_variant	Exon 10 of 29	2		ENSP00000405002.2
ABCC6	ENST00000622290.5 link	n.1245G>A		non_coding_transcript_exon_variant	Exon 10 of 32	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45196

AN:

152046

Hom.:

7122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.371

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.0959

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.306

GnomAD2 exomes

AF:

0.285

AC:

70039

AN:

245644

AF XY:

0.286

show subpopulations

Gnomad AFR exome

AF:

0.256

Gnomad AMR exome

AF:

0.263

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.0947

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.326

AC:

475529

AN:

1459470

Hom.:

80315

Cov.:

AF XY:

0.323

AC XY:

234251

AN XY:

725842

show subpopulations

African (AFR)

AF:

0.249

AC:

8332

AN:

33462

American (AMR)

AF:

0.269

AC:

11945

AN:

44404

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

5803

AN:

26070

East Asian (EAS)

AF:

0.0903

AC:

3580

AN:

39646

South Asian (SAS)

AF:

0.219

AC:

18836

AN:

85850

European-Finnish (FIN)

AF:

0.314

AC:

16681

AN:

53208

Middle Eastern (MID)

AF:

0.293

AC:

1691

AN:

5764

European-Non Finnish (NFE)

AF:

0.352

AC:

390803

AN:

1110788

Other (OTH)

AF:

0.296

AC:

17858

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

18246

36491

54737

72982

91228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12258

24516

36774

49032

61290

<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:

0.297

AC:

45189

AN:

152164

Hom.:

7118

Cov.:

AF XY:

0.291

AC XY:

21661

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.253

AC:

10507

AN:

41522

American (AMR)

AF:

0.294

AC:

4502

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

775

AN:

3472

East Asian (EAS)

AF:

0.0959

AC:

495

AN:

5160

South Asian (SAS)

AF:

0.207

AC:

997

AN:

4822

European-Finnish (FIN)

AF:

0.310

AC:

3283

AN:

10600

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.347

AC:

23578

AN:

67976

Other (OTH)

AF:

0.302

AC:

638

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1655

3311

4966

6622

8277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.319

Hom.:

16123

Bravo

AF:

0.294

Asia WGS

AF:

0.148

AC:

513

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive inherited pseudoxanthoma elasticum

Benign:2

Mar 01, 2021

PXE International

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:research

- -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Arterial calcification, generalized, of infancy, 2

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pseudoxanthoma elasticum, forme fruste

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive inherited pseudoxanthoma elasticum;C1867450:Pseudoxanthoma elasticum, forme fruste;C3276161:Arterial calcification, generalized, of infancy, 2

Benign:1

Aug 27, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.4

(source)

DANN

Benign

0.47

PhyloP100

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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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