rs3213473

Variant names:

• chr16-16162910-T-A
• rs3213473
• NM_001171.6:c.3506+83A>T

Your query was ambiguous. Multiple possible variants found:

• chr16-16162910-T-A
• chr16-16162910-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001171.6(ABCC6):​c.3506+83A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,574,632 control chromosomes in the GnomAD database, including 279 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 0.012 (12 hom., cov: 31)
  • Exomes 𝑓: 0.017 (267 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 16 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=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0116 (1762/152108) while in subpopulation NFE AF = 0.0181 (1229/67968). AF 95% confidence interval is 0.0172. There are 12 homozygotes in GnomAd4. There are 847 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.3506+83A>T		intron_variant	Intron 24 of 30	ENST00000205557.12	NP_001162.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.3506+83A>T		intron_variant	Intron 24 of 30	1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6	n.*516-1346A>T		intron_variant	Intron 22 of 28	2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.3506+83A>T		intron_variant	Intron 24 of 31	5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1761 AN: 151990 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0101

GnomAD4 exome AF: 0.0172 AC: 24400 AN: 1422524 Hom.: 267 AF XY: 0.0167 AC XY: 11876 AN XY: 710076

African (AFR) AF: 0.00233 AC: 76 AN: 32588

American (AMR) AF: 0.00618 AC: 276 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00668 AC: 173 AN: 25912

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39532

South Asian (SAS) AF: 0.00581 AC: 496 AN: 85384

European-Finnish (FIN) AF: 0.0198 AC: 1034 AN: 52318

Middle Eastern (MID) AF: 0.00195 AC: 9 AN: 4606

European-Non Finnish (NFE) AF: 0.0199 AC: 21408 AN: 1078482

Other (OTH) AF: 0.0157 AC: 927 AN: 59018

GnomAD4 genome AF: 0.0116 AC: 1762 AN: 152108 Hom.: 12 Cov.: 31 AF XY: 0.0114 AC XY: 847 AN XY: 74360

African (AFR) AF: 0.00325 AC: 135 AN: 41482

American (AMR) AF: 0.00622 AC: 95 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4826

European-Finnish (FIN) AF: 0.0215 AC: 228 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0181 AC: 1229 AN: 67968

Other (OTH) AF: 0.00997 AC: 21 AN: 2106

Alfa AF: 0.000384 Hom.: 83252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.1
DANN	Benign	0.76
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism

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: rs3213473; hg19: chr16-16256767;