7-87539433-C-T

Variant names:

• chr7-87539433-C-T
• rs4728699
• NM_001348946.2:c.2320-88G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348946.2(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 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.2320-88G>A		intron_variant	Intron 18 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.2530-88G>A		intron_variant	Intron 22 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.2320-88G>A		intron_variant	Intron 19 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.2320-88G>A		intron_variant	Intron 20 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.2320-88G>A		intron_variant	Intron 18 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.2320-88G>A		intron_variant	Intron 19 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.2128-88G>A		intron_variant	Intron 18 of 27	5		ENSP00000444095.1

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

African (AFR) AF: 0.994 AC: 27918 AN: 28090

American (AMR) AF: 0.981 AC: 38745 AN: 39500

Ashkenazi Jewish (ASJ) AF: 0.967 AC: 23187 AN: 23978

East Asian (EAS) AF: 1.00 AC: 37913 AN: 37920

South Asian (SAS) AF: 0.931 AC: 72180 AN: 77534

European-Finnish (FIN) AF: 0.946 AC: 47931 AN: 50656

Middle Eastern (MID) AF: 0.968 AC: 5045 AN: 5214

European-Non Finnish (NFE) AF: 0.954 AC: 824869 AN: 864940

Other (OTH) AF: 0.961 AC: 49095 AN: 51084

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

African (AFR) AF: 0.992 AC: 41242 AN: 41570

American (AMR) AF: 0.972 AC: 14881 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.966 AC: 3354 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5166 AN: 5172

South Asian (SAS) AF: 0.933 AC: 4508 AN: 4830

European-Finnish (FIN) AF: 0.948 AC: 10071 AN: 10622

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 64957 AN: 68038

Other (OTH) AF: 0.974 AC: 2062 AN: 2116

Alfa AF: 0.963 Hom.: 105409

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
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4728699; hg19: chr7-87168749; COSMIC: COSV106051978; COSMIC: COSV106051978;