NM_001348946.2:c.69-76C>T

Variant names:

• chr7-87595890-G-A
• rs58898486
• NM_001348946.2:c.69-76C>T

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.69-76C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000982 in 1,018,390 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 9.8e-7 (0 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654
• Publications: 0 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=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.69-76C>T		intron_variant	Intron 2 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.279-76C>T		intron_variant	Intron 6 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.69-76C>T		intron_variant	Intron 3 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.69-76C>T		intron_variant	Intron 4 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.69-76C>T		intron_variant	Intron 2 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.69-76C>T		intron_variant	Intron 3 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.69-76C>T		intron_variant	Intron 3 of 27	5		ENSP00000444095.1
ABCB1	ENST00000416177.1	c.69-76C>T		intron_variant	Intron 4 of 5	5		ENSP00000399419.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.82e-7 AC: 1 AN: 1018390 Hom.: 0 AF XY: 0.00000191 AC XY: 1 AN XY: 524348

African (AFR) AF: 0.00 AC: 0 AN: 23946

American (AMR) AF: 0.00 AC: 0 AN: 41668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22978

East Asian (EAS) AF: 0.00 AC: 0 AN: 35534

South Asian (SAS) AF: 0.00 AC: 0 AN: 73950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4016

European-Non Finnish (NFE) AF: 0.00000138 AC: 1 AN: 722338

Other (OTH) AF: 0.00 AC: 0 AN: 45142

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.20
DANN	Benign	0.36
PhyloP100		-0.65

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: rs58898486; hg19: chr7-87225206;