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 -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting 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. Variant has been reported in ClinVar as (no stars).

• 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: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Orphanet
• inherited pseudoxanthoma elasticum

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• arterial calcification of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 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. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 12 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	NM_001171.6	MANE Select	c.3506+83A>T		intron	N/A	NP_001162.5
	ABCC6	NM_001440309.1		c.3473+83A>T		intron	N/A	NP_001427238.1
	ABCC6	NM_001440310.1		c.3338+83A>T		intron	N/A	NP_001427239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	ENST00000205557.12	TSL:1 MANE Select	c.3506+83A>T		intron	N/A	ENSP00000205557.7	O95255-1
	ABCC6	ENST00000909083.1		c.3602+83A>T		intron	N/A	ENSP00000579142.1
	ABCC6	ENST00000909090.1		c.3599+83A>T		intron	N/A	ENSP00000579149.1

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 v4.9

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;