rs212097

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.4404-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,612,620 control chromosomes in the GnomAD database, including 147,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.36 ( 11290 hom., cov: 33)

Exomes 𝑓: 0.43 ( 135720 hom. )

Consequence

ABCC6
NM_001171.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0390

Publications

20 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: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Orphanet
inherited pseudoxanthoma elasticum
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 16-16150272-T-C is Benign according to our data. Variant chr16-16150272-T-C is described in ClinVar as Benign. ClinVar VariationId is 1245693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ABCC6	NM_001171.6	MANE Select	c.4404-31A>G	intron	N/A	NP_001162.5
ABCC6	NM_001440309.1		c.4371-31A>G	intron	N/A	NP_001427238.1
ABCC6	NM_001440310.1		c.4236-31A>G	intron	N/A	NP_001427239.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCC6	ENST00000205557.12	TSL:1 MANE Select	c.4404-31A>G	intron	N/A	ENSP00000205557.7	O95255-1
ABCC6	ENST00000909083.1		c.4500-31A>G	intron	N/A	ENSP00000579142.1
ABCC6	ENST00000909090.1		c.4497-31A>G	intron	N/A	ENSP00000579149.1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54653

AN:

152012

Hom.:

11287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.596

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.468

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.375

GnomAD2 exomes

AF:

0.395

AC:

97477

AN:

246794

AF XY:

0.400

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.406

Gnomad ASJ exome

AF:

0.433

Gnomad EAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.461

Gnomad NFE exome

AF:

0.455

Gnomad OTH exome

AF:

0.415

GnomAD4 exome

AF:

0.426

AC:

622079

AN:

1460490

Hom.:

135720

Cov.:

AF XY:

0.425

AC XY:

308969

AN XY:

726524

show subpopulations

African (AFR)

AF:

0.146

AC:

4885

AN:

33468

American (AMR)

AF:

0.410

AC:

18287

AN:

44550

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

11329

AN:

26126

East Asian (EAS)

AF:

0.208

AC:

8255

AN:

39688

South Asian (SAS)

AF:

0.358

AC:

30839

AN:

86212

European-Finnish (FIN)

AF:

0.450

AC:

23851

AN:

52956

Middle Eastern (MID)

AF:

0.374

AC:

2148

AN:

5750

European-Non Finnish (NFE)

AF:

0.448

AC:

498062

AN:

1111396

Other (OTH)

AF:

0.405

AC:

24423

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

21684

43369

65053

86738

108422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14750

29500

44250

59000

73750

<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:

0.359

AC:

54671

AN:

152130

Hom.:

11290

Cov.:

AF XY:

0.361

AC XY:

26822

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.160

AC:

6653

AN:

41532

American (AMR)

AF:

0.429

AC:

6549

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1522

AN:

3472

East Asian (EAS)

AF:

0.176

AC:

911

AN:

5166

South Asian (SAS)

AF:

0.356

AC:

1716

AN:

4822

European-Finnish (FIN)

AF:

0.468

AC:

4950

AN:

10578

Middle Eastern (MID)

AF:

0.384

AC:

112

AN:

292

European-Non Finnish (NFE)

AF:

0.455

AC:

30935

AN:

67970

Other (OTH)

AF:

0.371

AC:

782

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1728

3456

5185

6913

8641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.426

Hom.:

25215

Bravo

AF:

0.343

Asia WGS

AF:

0.276

AC:

964

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Arterial calcification, generalized, of infancy, 2 (1)

Autosomal recessive inherited pseudoxanthoma elasticum (1)

Pseudoxanthoma elasticum, forme fruste (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.1

(source)

DANN

Benign

0.75

PhyloP100

0.039

BranchPoint Hunter

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over