rs10276603

Variant names:

• chr7-87542211-T-C
• rs10276603
• NM_001348946.2:c.2212-747A>G

Variant summary

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

The NM_001348946.2(ABCB1):​c.2212-747A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,194 control chromosomes in the GnomAD database, including 1,248 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 0.12 (1248 hom., cov: 33)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.2212-747A>G		intron_variant	Intron 17 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.2422-747A>G		intron_variant	Intron 21 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.2212-747A>G		intron_variant	Intron 18 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.2212-747A>G		intron_variant	Intron 19 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.2212-747A>G		intron_variant	Intron 17 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.2212-747A>G		intron_variant	Intron 18 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.2020-747A>G		intron_variant	Intron 17 of 27	5		ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18921 AN: 152076 Hom.: 1243 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0601

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0474

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.125 AC: 18951 AN: 152194 Hom.: 1248 Cov.: 33 AF XY: 0.122 AC XY: 9083 AN XY: 74412

African (AFR) AF: 0.150 AC: 6229 AN: 41516

American (AMR) AF: 0.109 AC: 1662 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3466

East Asian (EAS) AF: 0.0598 AC: 310 AN: 5182

South Asian (SAS) AF: 0.148 AC: 712 AN: 4818

European-Finnish (FIN) AF: 0.0474 AC: 502 AN: 10594

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8518 AN: 68006

Other (OTH) AF: 0.121 AC: 256 AN: 2110

Alfa AF: 0.130 Hom.: 378

Bravo AF: 0.129

Asia WGS AF: 0.119 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.64
PhyloP100		0.18
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: rs10276603; hg19: chr7-87171527;