rs72664283

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001171.6(ABCC6):c.1077A>G(p.Ser359Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,610,970 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 38 hom., cov: 31)

Exomes 𝑓: 0.0027 ( 74 hom. )

Consequence

ABCC6
NM_001171.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.32

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-16202100-T-C is Benign according to our data. Variant chr16-16202100-T-C is described in ClinVar as [Benign]. Clinvar id is 379234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.32 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2031/152224) while in subpopulation AFR AF= 0.0395 (1639/41494). AF 95% confidence interval is 0.0379. There are 38 homozygotes in gnomad4. There are 1031 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ABCC6	NM_001171.6 link	c.1077A>G	p.Ser359Ser	synonymous_variant	Exon 9 of 31	ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1 link	c.735A>G	p.Ser245Ser	synonymous_variant	Exon 9 of 31		NP_001338729.1
ABCC6	NR_147784.1 link	n.1114A>G		non_coding_transcript_exon_variant	Exon 9 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12 link	c.1077A>G	p.Ser359Ser	synonymous_variant	Exon 9 of 31	1	NM_001171.6	ENSP00000205557.7		O95255-1

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2023

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0394

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00714

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00501

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00559

AC:

1402

AN:

250716

Hom.:

AF XY:

0.00526

AC XY:

713

AN XY:

135482

show subpopulations

Gnomad AFR exome

AF:

0.0374

Gnomad AMR exome

AF:

0.00458

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00256

Gnomad SAS exome

AF:

0.0121

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00157

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00274

AC:

4001

AN:

1458746

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

2142

AN XY:

725700

show subpopulations

Gnomad4 AFR exome

AF:

0.0298

Gnomad4 AMR exome

AF:

0.00513

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.00277

Gnomad4 SAS exome

AF:

0.0124

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.00488

GnomAD4 genome

AF:

0.0133

AC:

2031

AN:

152224

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1031

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0395

Gnomad4 AMR

AF:

0.00719

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00502

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00179

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00816

Hom.:

Bravo

AF:

0.0150

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

not specified

Benign:1

May 19, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

-0.89

CADD

Benign

0.64

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over