7-87539433-C-T

Position:

• chr7-87539433-C-T

Variant summary

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

The ENST00000622132.5(ABCB1):​c.2320-88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.957 in 1,331,250 control chromosomes in the GnomAD database, including 610,142 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 0.97 (71371 hom., cov: 33)
  • Exomes 𝑓: 0.96 (538771 hom.)
• Consequence: ABCB1 ENST00000622132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

Genes affected

ABCB1 (HGNC:40): (ATP binding cassette subfamily B member 1) The membrane-associated 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 MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.2320-88G>A		intron_variant		ENST00000622132.5	NP_001335875.1
ABCB1	NM_000927.5	c.2320-88G>A		intron_variant			NP_000918.2
ABCB1	NM_001348944.2	c.2320-88G>A		intron_variant			NP_001335873.1
ABCB1	NM_001348945.2	c.2530-88G>A		intron_variant			NP_001335874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.2320-88G>A		intron_variant		1	NM_001348946.2	ENSP00000478255	P1
ABCB1	ENST00000265724.8	c.2320-88G>A		intron_variant		1		ENSP00000265724	P1
ABCB1	ENST00000543898.5	c.2128-88G>A		intron_variant		5		ENSP00000444095

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147305 AN: 152216 Hom.: 71307 Cov.: 33

Gnomad AFR AF: 0.992

Gnomad AMI AF: 0.993

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.966

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.974

GnomAD4 exome AF: 0.956 AC: 1126883 AN: 1178916 Hom.: 538771 AF XY: 0.955 AC XY: 569568 AN XY: 596620

Gnomad4 AFR exome AF: 0.994

Gnomad4 AMR exome AF: 0.981

Gnomad4 ASJ exome AF: 0.967

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.931

Gnomad4 FIN exome AF: 0.946

Gnomad4 NFE exome AF: 0.954

Gnomad4 OTH exome AF: 0.961

GnomAD4 genome AF: 0.968 AC: 147428 AN: 152334 Hom.: 71371 Cov.: 33 AF XY: 0.967 AC XY: 72045 AN XY: 74496

Gnomad4 AFR AF: 0.992

Gnomad4 AMR AF: 0.972

Gnomad4 ASJ AF: 0.966

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.948

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.974

Alfa AF: 0.958 Hom.: 66955

Bravo AF: 0.972

Asia WGS AF: 0.976 AC: 3396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.013
DANN	Benign	0.39

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: rs4728699; hg19: chr7-87168749;