chr7-87521774-T-C

Variant names:

• chr7-87521774-T-C
• rs4148743
• NM_001348946.2:c.2686-898A>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.2686-898A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 812,910 control chromosomes in the GnomAD database, including 98,811 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 0.52 (21401 hom., cov: 32)
  • Exomes 𝑓: 0.47 (77410 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.11
• Publications: 11 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]

HNRNPA1P9 (HGNC:39127): (heterogeneous nuclear ribonucleoprotein A1 pseudogene 9)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348946.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.2686-898A>G		intron	N/A	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.2896-898A>G		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.2686-898A>G		intron	N/A	NP_000918.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.2686-898A>G		intron	N/A	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.2686-898A>G		intron	N/A	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000488737.6	TSL:1	n.328-898A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79483 AN: 151872 Hom.: 21365 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.545

GnomAD4 exome AF: 0.473 AC: 312911 AN: 660920 Hom.: 77410 Cov.: 7 AF XY: 0.467 AC XY: 167326 AN XY: 358082

African (AFR) AF: 0.613 AC: 11351 AN: 18514

American (AMR) AF: 0.422 AC: 18373 AN: 43492

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 12544 AN: 21186

East Asian (EAS) AF: 0.216 AC: 7804 AN: 36156

South Asian (SAS) AF: 0.322 AC: 22746 AN: 70718

European-Finnish (FIN) AF: 0.445 AC: 16612 AN: 37322

Middle Eastern (MID) AF: 0.504 AC: 1343 AN: 2664

European-Non Finnish (NFE) AF: 0.517 AC: 205113 AN: 396632

Other (OTH) AF: 0.497 AC: 17025 AN: 34236

GnomAD4 genome AF: 0.524 AC: 79571 AN: 151990 Hom.: 21401 Cov.: 32 AF XY: 0.515 AC XY: 38245 AN XY: 74290

African (AFR) AF: 0.609 AC: 25252 AN: 41478

American (AMR) AF: 0.495 AC: 7559 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2042 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1143 AN: 5174

South Asian (SAS) AF: 0.323 AC: 1554 AN: 4810

European-Finnish (FIN) AF: 0.440 AC: 4639 AN: 10532

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35540 AN: 67948

Other (OTH) AF: 0.541 AC: 1144 AN: 2114

Alfa AF: 0.516 Hom.: 2965

Bravo AF: 0.531

Asia WGS AF: 0.318 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.1
DANN	Benign	0.34
PhyloP100		3.1
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: rs4148743; hg19: chr7-87151090; COSMIC: COSV55959175; COSMIC: COSV55959175;