rs72664282

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.645G>A(p.Thr215Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 1,003,146 control chromosomes in the GnomAD database, including 1,681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 215 hom., cov: 21)

Exomes 𝑓: 0.052 ( 1466 hom. )

Consequence

ABCC6
NM_001171.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.419

Publications

3 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:

ENSG00000305554 (HGNC:):

ENSG00000305554 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 16-16212202-C-T is Benign according to our data. Variant chr16-16212202-C-T is described in ClinVar as [Benign]. Clinvar id is 433208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.419 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6 link	c.645G>A	p.Thr215Thr	synonymous_variant	Exon 6 of 31	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12 link	c.645G>A	p.Thr215Thr	synonymous_variant	Exon 6 of 31	1	NM_001171.6	ENSP00000205557.7		O95255-1

Frequencies

GnomAD3 genomes

AF:

0.0438

AC:

6136

AN:

140068

Hom.:

216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0260

Gnomad ASJ

AF:

0.0428

Gnomad EAS

AF:

0.000209

Gnomad SAS

AF:

0.0113

Gnomad FIN

AF:

0.0593

Gnomad MID

AF:

0.00658

Gnomad NFE

AF:

0.0673

Gnomad OTH

AF:

0.0338

GnomAD2 exomes

AF:

0.0401

AC:

6470

AN:

161180

AF XY:

0.0405

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0207

Gnomad ASJ exome

AF:

0.0383

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0537

Gnomad NFE exome

AF:

0.0657

Gnomad OTH exome

AF:

0.0427

GnomAD4 exome

AF:

0.0523

AC:

45140

AN:

863000

Hom.:

1466

Cov.:

AF XY:

0.0511

AC XY:

23043

AN XY:

451024

show subpopulations

African (AFR)

AF:

0.0109

AC:

219

AN:

20164

American (AMR)

AF:

0.0205

AC:

841

AN:

41056

Ashkenazi Jewish (ASJ)

AF:

0.0386

AC:

851

AN:

22046

East Asian (EAS)

AF:

0.00

AC:

AN:

36100

South Asian (SAS)

AF:

0.0124

AC:

903

AN:

72824

European-Finnish (FIN)

AF:

0.0590

AC:

3085

AN:

52288

Middle Eastern (MID)

AF:

0.00921

AC:

AN:

4562

European-Non Finnish (NFE)

AF:

0.0652

AC:

37374

AN:

573618

Other (OTH)

AF:

0.0452

AC:

1825

AN:

40342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1919

3838

5758

7677

9596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0438

AC:

6135

AN:

140146

Hom.:

215

Cov.:

AF XY:

0.0411

AC XY:

2785

AN XY:

67786

show subpopulations

African (AFR)

AF:

0.0123

AC:

437

AN:

35648

American (AMR)

AF:

0.0258

AC:

361

AN:

13966

Ashkenazi Jewish (ASJ)

AF:

0.0428

AC:

143

AN:

3338

East Asian (EAS)

AF:

0.000209

AC:

AN:

4776

South Asian (SAS)

AF:

0.0113

AC:

AN:

4408

European-Finnish (FIN)

AF:

0.0593

AC:

574

AN:

9684

Middle Eastern (MID)

AF:

0.00709

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0673

AC:

4394

AN:

65258

Other (OTH)

AF:

0.0334

AC:

AN:

1914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

233

466

698

931

1164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0504

Hom.:

Bravo

AF:

0.0379

ClinVar

Significance: Benign

Submissions summary: Benign:7

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

- -

Dec 31, 2019

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

- -

Pseudoxanthoma elasticum, forme fruste

Benign:1

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

9.4

(source)

DANN

Benign

0.54

PhyloP100

-0.42

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

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rs72664282

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