7-87504677-T-C

Variant names:

• chr7-87504677-T-C
• rs1186746
• NM_001348946.2:c.3637-228A>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.3637-228A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,768 control chromosomes in the GnomAD database, including 3,668 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 0.21 (3668 hom., cov: 30)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.3637-228A>G		intron_variant	Intron 27 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.3847-228A>G		intron_variant	Intron 31 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.3637-228A>G		intron_variant	Intron 28 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.3637-228A>G		intron_variant	Intron 29 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.3637-228A>G		intron_variant	Intron 27 of 27	1	NM_001348946.2	ENSP00000478255.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32192 AN: 151650 Hom.: 3663 Cov.: 30

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.212 AC: 32220 AN: 151768 Hom.: 3668 Cov.: 30 AF XY: 0.209 AC XY: 15534 AN XY: 74162

African (AFR) AF: 0.156 AC: 6443 AN: 41390

American (AMR) AF: 0.175 AC: 2676 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3468

East Asian (EAS) AF: 0.167 AC: 853 AN: 5108

South Asian (SAS) AF: 0.218 AC: 1043 AN: 4790

European-Finnish (FIN) AF: 0.187 AC: 1969 AN: 10524

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.259 AC: 17613 AN: 67912

Other (OTH) AF: 0.211 AC: 445 AN: 2110

Alfa AF: 0.109 Hom.: 180

Bravo AF: 0.209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.28
DANN	Benign	0.072
PhyloP100		-1.8
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: rs1186746; hg19: chr7-87133993;