7-87585798-A-T

Variant names:

• chr7-87585798-A-T
• rs1211152
• NM_001348946.2:c.118-118T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001348946.2(ABCB1):​c.118-118T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 11 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.118-118T>A		intron_variant	Intron 3 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.328-118T>A		intron_variant	Intron 7 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.118-118T>A		intron_variant	Intron 4 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.118-118T>A		intron_variant	Intron 5 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.118-118T>A		intron_variant	Intron 3 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.118-118T>A		intron_variant	Intron 4 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.118-118T>A		intron_variant	Intron 4 of 27	5		ENSP00000444095.1
ABCB1	ENST00000416177.1	c.118-118T>A		intron_variant	Intron 5 of 5	5		ENSP00000399419.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000234 AC: 2 AN: 855518 Hom.: 0 AF XY: 0.00000454 AC XY: 2 AN XY: 440490

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20880

American (AMR) AF: 0.00 AC: 0 AN: 32540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20390

East Asian (EAS) AF: 0.00 AC: 0 AN: 33338

South Asian (SAS) AF: 0.00 AC: 0 AN: 64580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4210

European-Non Finnish (NFE) AF: 0.00000330 AC: 2 AN: 605782

Other (OTH) AF: 0.00 AC: 0 AN: 40094

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.38
DANN	Benign	0.63
PhyloP100		-1.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1211152; hg19: chr7-87215114;