chr7-87534913-T-C

Variant names:

• chr7-87534913-T-C
• rs11972405
• NM_001348946.2:c.2481+1545A>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.2481+1545A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 111,204 control chromosomes in the GnomAD database, including 1,271 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 0.16 (1271 hom., cov: 21)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.2481+1545A>G		intron_variant	Intron 20 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.2691+1545A>G		intron_variant	Intron 24 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.2481+1545A>G		intron_variant	Intron 21 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.2481+1545A>G		intron_variant	Intron 22 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.2481+1545A>G		intron_variant	Intron 20 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.2481+1545A>G		intron_variant	Intron 21 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.2289+1545A>G		intron_variant	Intron 20 of 27	5		ENSP00000444095.1
ABCB1	ENST00000496821.5	n.109+1545A>G		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 17959 AN: 111168 Hom.: 1266 Cov.: 21

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.162 AC: 17980 AN: 111204 Hom.: 1271 Cov.: 21 AF XY: 0.160 AC XY: 8473 AN XY: 52938

African (AFR) AF: 0.255 AC: 6155 AN: 24132

American (AMR) AF: 0.138 AC: 1439 AN: 10408

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 507 AN: 3032

East Asian (EAS) AF: 0.129 AC: 273 AN: 2120

South Asian (SAS) AF: 0.171 AC: 613 AN: 3588

European-Finnish (FIN) AF: 0.0528 AC: 316 AN: 5984

Middle Eastern (MID) AF: 0.187 AC: 40 AN: 214

European-Non Finnish (NFE) AF: 0.138 AC: 8205 AN: 59398

Other (OTH) AF: 0.154 AC: 235 AN: 1522

Alfa AF: 0.0481 Hom.: 45

Bravo AF: 0.136

Asia WGS AF: 0.124 AC: 421 AN: 3404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.62
PhyloP100		0.57
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: rs11972405; hg19: chr7-87164229;