rs2283508

Positions:

• chr16-16178651-G-A

Variant summary

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

The NM_001171.6(ABCC6):​c.2415+147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 916,704 control chromosomes in the GnomAD database, including 106,362 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 0.45 (16149 hom., cov: 31)
  • Exomes 𝑓: 0.47 (90213 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.2415+147C>T		intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.2073+147C>T		intron_variant
ABCC6	NR_147784.1	n.2452+147C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.2415+147C>T		intron_variant		1	NM_001171.6	P1
ABCC6	ENST00000456970.6	c.2415+147C>T		intron_variant, NMD_transcript_variant		2
ABCC6	ENST00000622290.5	c.2415+147C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68690 AN: 151716 Hom.: 16148 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.442

GnomAD4 exome AF: 0.475 AC: 363017 AN: 764870 Hom.: 90213 AF XY: 0.466 AC XY: 188694 AN XY: 405000

Gnomad4 AFR exome AF: 0.379

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.300

Gnomad4 FIN exome AF: 0.502

Gnomad4 NFE exome AF: 0.527

Gnomad4 OTH exome AF: 0.460

GnomAD4 genome AF: 0.453 AC: 68708 AN: 151834 Hom.: 16149 Cov.: 31 AF XY: 0.445 AC XY: 33028 AN XY: 74196

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.437

Alfa AF: 0.500 Hom.: 26188

Bravo AF: 0.449

Asia WGS AF: 0.225 AC: 781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.55

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: rs2283508; hg19: chr16-16272508; COSMIC: COSV52748054; COSMIC: COSV52748054;