chr16-16195675-T-C

Variant names:

• chr16-16195675-T-C
• rs8056397
• NM_001171.6:c.1338+2346A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001171.6(ABCC6):​c.1338+2346A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,830 control chromosomes in the GnomAD database, including 23,524 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23524 hom., cov: 30)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.1338+2346A>G		intron_variant	Intron 10 of 30	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.1338+2346A>G		intron_variant	Intron 10 of 30	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000574094.6	c.1339-860A>G		intron_variant	Intron 10 of 10	5		ENSP00000507301.1
ABCC6	ENST00000456970.6	n.1338+2346A>G		intron_variant	Intron 10 of 28	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.1338+2346A>G		intron_variant	Intron 10 of 31	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81505 AN: 151712 Hom.: 23523 Cov.: 30

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.537 AC: 81520 AN: 151830 Hom.: 23524 Cov.: 30 AF XY: 0.526 AC XY: 39002 AN XY: 74180

African (AFR) AF: 0.375 AC: 15543 AN: 41402

American (AMR) AF: 0.537 AC: 8192 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2113 AN: 3464

East Asian (EAS) AF: 0.167 AC: 860 AN: 5152

South Asian (SAS) AF: 0.406 AC: 1950 AN: 4808

European-Finnish (FIN) AF: 0.538 AC: 5654 AN: 10516

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45102 AN: 67948

Other (OTH) AF: 0.567 AC: 1188 AN: 2094

Alfa AF: 0.608 Hom.: 83348

Bravo AF: 0.531

Asia WGS AF: 0.309 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.45
PhyloP100		-0.61
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: rs8056397; hg19: chr16-16289532;