chr16-16196520-C-T

Position:

• chr16-16196520-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001171.6(ABCC6):​c.1338+1501G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,088 control chromosomes in the GnomAD database, including 34,676 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 0.67 (34676 hom., cov: 31)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.1338+1501G>A		intron_variant		ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.996+1501G>A		intron_variant			NP_001338729.1
ABCC6	NR_147784.1	n.1375+1501G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.1338+1501G>A		intron_variant		1	NM_001171.6	ENSP00000205557	P1
ABCC6	ENST00000574094.6	c.1338+1501G>A		intron_variant		5		ENSP00000507301
ABCC6	ENST00000456970.6	c.1338+1501G>A		intron_variant, NMD_transcript_variant		2		ENSP00000405002
ABCC6	ENST00000622290.5	c.1338+1501G>A		intron_variant, NMD_transcript_variant		5		ENSP00000483331

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102415 AN: 151970 Hom.: 34641 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.674 AC: 102502 AN: 152088 Hom.: 34676 Cov.: 31 AF XY: 0.675 AC XY: 50168 AN XY: 74356

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.676

Alfa AF: 0.690 Hom.: 38998

Bravo AF: 0.666

Asia WGS AF: 0.713 AC: 2477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.49

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: rs4780599; hg19: chr16-16290377;