7-87515097-G-C

Variant names:

• chr7-87515097-G-C
• rs4148749
• NM_001348946.2:c.3282+134C>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.3282+134C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 1,169,926 control chromosomes in the GnomAD database, including 1,356 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 0.053 (347 hom., cov: 32)
  • Exomes 𝑓: 0.032 (1009 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.3282+134C>G		intron_variant	Intron 25 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.3492+134C>G		intron_variant	Intron 29 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.3282+134C>G		intron_variant	Intron 26 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.3282+134C>G		intron_variant	Intron 27 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.3282+134C>G		intron_variant	Intron 25 of 27	1	NM_001348946.2	ENSP00000478255.1

Frequencies

GnomAD3 genomes AF: 0.0532 AC: 8089 AN: 152160 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0435

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0483

GnomAD4 exome AF: 0.0316 AC: 32160 AN: 1017648 Hom.: 1009 AF XY: 0.0317 AC XY: 16299 AN XY: 514488

African (AFR) AF: 0.108 AC: 2638 AN: 24398

American (AMR) AF: 0.0564 AC: 1930 AN: 34194

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 513 AN: 21450

East Asian (EAS) AF: 0.156 AC: 5313 AN: 34014

South Asian (SAS) AF: 0.0457 AC: 3079 AN: 67406

European-Finnish (FIN) AF: 0.0366 AC: 1247 AN: 34090

Middle Eastern (MID) AF: 0.0270 AC: 90 AN: 3330

European-Non Finnish (NFE) AF: 0.0209 AC: 15752 AN: 753100

Other (OTH) AF: 0.0350 AC: 1598 AN: 45666

GnomAD4 genome AF: 0.0532 AC: 8099 AN: 152278 Hom.: 347 Cov.: 32 AF XY: 0.0537 AC XY: 3996 AN XY: 74478

African (AFR) AF: 0.105 AC: 4380 AN: 41546

American (AMR) AF: 0.0435 AC: 666 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3470

East Asian (EAS) AF: 0.137 AC: 707 AN: 5176

South Asian (SAS) AF: 0.0499 AC: 241 AN: 4832

European-Finnish (FIN) AF: 0.0311 AC: 330 AN: 10626

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0222 AC: 1512 AN: 68014

Other (OTH) AF: 0.0497 AC: 105 AN: 2112

Alfa AF: 0.0166 Hom.: 17

Bravo AF: 0.0574

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.36
PhyloP100		-0.30
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: rs4148749; hg19: chr7-87144413;