rs8058696

Variant names:

• chr16-16185012-G-C
• rs8058696
• NM_001171.6:c.1890C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-16185012-G-C
• chr16-16185012-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001171.6(ABCC6):​c.1890C>G​(p.Thr630Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,608,362 control chromosomes in the GnomAD database, including 178,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14341 hom., cov: 31)
  • Exomes 𝑓: 0.47 (164519 hom.)
• Consequence: ABCC6 NM_001171.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.551
• Publications: 29 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-16185012-G-C is Benign according to our data. Variant chr16-16185012-G-C is described in ClinVar as Benign. ClinVar VariationId is 433246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.551 with no splicing effect.
• 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	c.1890C>G	p.Thr630Thr	synonymous_variant	Exon 15 of 31	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.1890C>G	p.Thr630Thr	synonymous_variant	Exon 15 of 31	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6	n.1890C>G		non_coding_transcript_exon_variant	Exon 15 of 29	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.1890C>G		non_coding_transcript_exon_variant	Exon 15 of 32	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64710 AN: 151562 Hom.: 14340 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.424

GnomAD2 exomes AF: 0.419 AC: 105062 AN: 251026 AF XY: 0.412

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: 0.446

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.444

GnomAD4 exome AF: 0.468 AC: 681196 AN: 1456680 Hom.: 164519 Cov.: 49 AF XY: 0.461 AC XY: 334274 AN XY: 724862

African (AFR) AF: 0.349 AC: 11654 AN: 33364

American (AMR) AF: 0.467 AC: 20884 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 11174 AN: 26092

East Asian (EAS) AF: 0.186 AC: 7392 AN: 39684

South Asian (SAS) AF: 0.261 AC: 22469 AN: 86188

European-Finnish (FIN) AF: 0.454 AC: 24220 AN: 53352

Middle Eastern (MID) AF: 0.352 AC: 2026 AN: 5758

European-Non Finnish (NFE) AF: 0.501 AC: 555077 AN: 1107346

Other (OTH) AF: 0.437 AC: 26300 AN: 60220

GnomAD4 genome AF: 0.427 AC: 64721 AN: 151682 Hom.: 14341 Cov.: 31 AF XY: 0.417 AC XY: 30889 AN XY: 74126

African (AFR) AF: 0.353 AC: 14622 AN: 41376

American (AMR) AF: 0.443 AC: 6753 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1472 AN: 3466

East Asian (EAS) AF: 0.158 AC: 813 AN: 5158

South Asian (SAS) AF: 0.250 AC: 1204 AN: 4816

European-Finnish (FIN) AF: 0.436 AC: 4586 AN: 10520

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.499 AC: 33808 AN: 67794

Other (OTH) AF: 0.419 AC: 884 AN: 2110

Alfa AF: 0.459 Hom.: 11900

Bravo AF: 0.428

Asia WGS AF: 0.210 AC: 730 AN: 3478

EpiCase AF: 0.483

EpiControl AF: 0.478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

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

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: 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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.32
PhyloP100		-0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8058696; hg19: chr16-16278869; COSMIC: COSV52741428;