rs2239319

chr16-16214494-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001171.6(ABCC6):c.475-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,551,506 control chromosomes in the GnomAD database, including 2,883 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.028 (353 hom., cov: 29)
  • Exomes 𝑓: 0.026 (2530 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-16214494-G-A is Benign according to our data. Variant chr16-16214494-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.475-45C>T		intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.133-45C>T		intron_variant
ABCC6	NR_147784.1	n.512-45C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.475-45C>T		intron_variant		1	NM_001171.6	P1

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4253 AN: 152144 Hom.: 353 Cov.: 29

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0397

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.00668

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.0273

GnomAD3 exomes AF: 0.0580 AC: 9010 AN: 155428 Hom.: 781 AF XY: 0.0586 AC XY: 4808 AN XY: 82072

Gnomad AFR exome AF: 0.0122

Gnomad AMR exome AF: 0.0822

Gnomad ASJ exome AF: 0.0194

Gnomad EAS exome AF: 0.322

Gnomad SAS exome AF: 0.0915

Gnomad FIN exome AF: 0.00462

Gnomad NFE exome AF: 0.0125

Gnomad OTH exome AF: 0.0351

GnomAD4 exome AF: 0.0262 AC: 36665 AN: 1399244 Hom.: 2530 Cov.: 32 AF XY: 0.0280 AC XY: 19318 AN XY: 690138

Gnomad4 AFR exome AF: 0.0114

Gnomad4 AMR exome AF: 0.0746

Gnomad4 ASJ exome AF: 0.0180

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.0905

Gnomad4 FIN exome AF: 0.00519

Gnomad4 NFE exome AF: 0.0112

Gnomad4 OTH exome AF: 0.0375

GnomAD4 genome AF: 0.0280 AC: 4256 AN: 152262 Hom.: 353 Cov.: 29 AF XY: 0.0317 AC XY: 2358 AN XY: 74442

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0398

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.00668

Gnomad4 NFE AF: 0.0105

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0167 Hom.: 15

Bravo AF: 0.0320

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.3
Dann	Benign	0.70

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: rs2239319; hg19: chr16-16308351;