rs212098

Positions:

• chr16-16150317-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001171.6(ABCC6):​c.4404-76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,601,114 control chromosomes in the GnomAD database, including 18,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1399 hom., cov: 33)
  • Exomes 𝑓: 0.15 (16640 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.30

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-16150317-T-C is Benign according to our data. Variant chr16-16150317-T-C is described in ClinVar as [Benign]. Clinvar id is 1225077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-16150317-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.4404-76A>G		intron_variant		ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.4062-76A>G		intron_variant			NP_001338729.1
ABCC6	NR_147784.1	n.4066-76A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.4404-76A>G		intron_variant		1	NM_001171.6	ENSP00000205557.7
ABCC6	ENST00000456970.6	n.*1413-76A>G		intron_variant		2		ENSP00000405002.2
ABCC6	ENST00000622290.5	n.*576-76A>G		intron_variant		5		ENSP00000483331.2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20224 AN: 152124 Hom.: 1399 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.0723

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.148 AC: 214232 AN: 1448872 Hom.: 16640 AF XY: 0.146 AC XY: 105003 AN XY: 720024

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.0969

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.0758

Gnomad4 FIN exome AF: 0.117

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.133 AC: 20221 AN: 152242 Hom.: 1399 Cov.: 33 AF XY: 0.132 AC XY: 9842 AN XY: 74440

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.0719

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.140

Alfa AF: 0.143 Hom.: 1654

Bravo AF: 0.134

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.16
DANN	Benign	0.62

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: rs212098; hg19: chr16-16244174; COSMIC: COSV52741910;