rs57745014

Positions:

• chr16-16155077-T-C
• chr16-16155077-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001171.6(ABCC6):​c.3883-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,533,288 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (25 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High Homozygotes in GnomAdExome4 at 25 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.3883-46A>G		intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.3541-46A>G		intron_variant
ABCC6	NR_147784.1	n.3545-46A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.3883-46A>G		intron_variant		1	NM_001171.6	P1
ABCC6	ENST00000576204.6	n.700A>G		non_coding_transcript_exon_variant	1/2	5
ABCC6	ENST00000456970.6	c.*892-46A>G		intron_variant, NMD_transcript_variant		2
ABCC6	ENST00000622290.5	c.*55-46A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00275 AC: 418 AN: 152154 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00422

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00318 AC: 454 AN: 142966 Hom.: 2 AF XY: 0.00299 AC XY: 230 AN XY: 76826

Gnomad AFR exome AF: 0.000387

Gnomad AMR exome AF: 0.000690

Gnomad ASJ exome AF: 0.0117

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000971

Gnomad FIN exome AF: 0.00507

Gnomad NFE exome AF: 0.00461

Gnomad OTH exome AF: 0.00352

GnomAD4 exome AF: 0.00382 AC: 5270 AN: 1381016 Hom.: 25 Cov.: 31 AF XY: 0.00376 AC XY: 2555 AN XY: 679548

Gnomad4 AFR exome AF: 0.000382

Gnomad4 AMR exome AF: 0.000732

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00110

Gnomad4 FIN exome AF: 0.00666

Gnomad4 NFE exome AF: 0.00410

Gnomad4 OTH exome AF: 0.00331

GnomAD4 genome AF: 0.00275 AC: 418 AN: 152272 Hom.: 0 Cov.: 31 AF XY: 0.00267 AC XY: 199 AN XY: 74454

Gnomad4 AFR AF: 0.000530

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00565

Gnomad4 NFE AF: 0.00422

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00481 Hom.: 0

Bravo AF: 0.00221

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

ABCC6: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.011
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs57745014; hg19: chr16-16248934;