NM_001348946.2:c.118-4485C>G

Variant names:

• chr7-87590165-G-C
• rs13229143
• NM_001348946.2:c.118-4485C>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.118-4485C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,066 control chromosomes in the GnomAD database, including 14,717 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 0.41 (14717 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• Publications: 9 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.118-4485C>G		intron_variant	Intron 3 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.328-4485C>G		intron_variant	Intron 7 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.118-4485C>G		intron_variant	Intron 4 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.118-4485C>G		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.118-4485C>G		intron_variant	Intron 3 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.118-4485C>G		intron_variant	Intron 4 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.118-4485C>G		intron_variant	Intron 4 of 27	5		ENSP00000444095.1
ABCB1	ENST00000416177.1	c.118-4485C>G		intron_variant	Intron 5 of 5	5		ENSP00000399419.1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62136 AN: 151948 Hom.: 14728 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.409 AC: 62122 AN: 152066 Hom.: 14717 Cov.: 32 AF XY: 0.413 AC XY: 30667 AN XY: 74322

African (AFR) AF: 0.157 AC: 6509 AN: 41470

American (AMR) AF: 0.418 AC: 6397 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1457 AN: 3466

East Asian (EAS) AF: 0.477 AC: 2470 AN: 5180

South Asian (SAS) AF: 0.651 AC: 3133 AN: 4814

European-Finnish (FIN) AF: 0.505 AC: 5330 AN: 10546

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35339 AN: 67978

Other (OTH) AF: 0.411 AC: 868 AN: 2112

Alfa AF: 0.449 Hom.: 2059

Bravo AF: 0.390

Asia WGS AF: 0.542 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.3
DANN	Benign	0.84
PhyloP100		0.21
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: rs13229143; hg19: chr7-87219481;