chr17-50672161-A-T

Position:

• chr17-50672161-A-T

Variant summary

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

The NM_003786.4(ABCC3):​c.2242-810A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,934 control chromosomes in the GnomAD database, including 33,439 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 0.66 (33439 hom., cov: 31)
• Consequence: ABCC3 NM_003786.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631

Genes affected

ABCC3 (HGNC:54): (ATP binding cassette subfamily C member 3) 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). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. The specific function of this protein has not yet been determined; however, this protein may play a role in the transport of biliary and intestinal excretion of organic anions. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC3	NM_003786.4	c.2242-810A>T		intron_variant		ENST00000285238.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC3	ENST00000285238.13	c.2242-810A>T		intron_variant		1	NM_003786.4	P1
ABCC3	ENST00000502426.5	c.*764-810A>T		intron_variant, NMD_transcript_variant		2
ABCC3	ENST00000505699.5	c.2242-810A>T		intron_variant, NMD_transcript_variant		2
ABCC3	ENST00000503304.1	n.393-810A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100547 AN: 151816 Hom.: 33409 Cov.: 31

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.662 AC: 100617 AN: 151934 Hom.: 33439 Cov.: 31 AF XY: 0.664 AC XY: 49315 AN XY: 74234

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.666

Alfa AF: 0.656 Hom.: 4088

Bravo AF: 0.664

Asia WGS AF: 0.676 AC: 2353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.40

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: rs8075406; hg19: chr17-48749522;