rs3213473

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.3506+83A>T		intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.3164+83A>T		intron_variant
ABCC6	NR_147784.1	n.3169-1346A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.3506+83A>T		intron_variant		1	NM_001171.6	P1
ABCC6	ENST00000456970.6	c.*516-1346A>T		intron_variant, NMD_transcript_variant		2
ABCC6	ENST00000622290.5	c.3506+83A>T		intron_variant, NMD_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.00233

Gnomad4 AMR exome AF: 0.00618

Gnomad4 ASJ exome AF: 0.00668

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00581

Gnomad4 FIN exome AF: 0.0198

Gnomad4 NFE exome AF: 0.0199

Gnomad4 OTH exome AF: 0.0157

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

Gnomad4 AFR AF: 0.00325

Gnomad4 AMR AF: 0.00622

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0215

Gnomad4 NFE AF: 0.0181

Gnomad4 OTH AF: 0.00997

Alfa AF: 0.000487 Hom.: 67554

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

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

Other links and lift over

dbSNP: rs3213473; hg19: chr16-16256767;