rs4148744

Variant names:

• chr7-87521458-G-A
• rs4148744
• NM_001348946.2:c.2686-582C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348946.2(ABCB1):​c.2686-582C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 711,330 control chromosomes in the GnomAD database, including 7,919 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 0.15 (3273 hom., cov: 32)
  • Exomes 𝑓: 0.084 (4646 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.23
• 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]

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 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.2686-582C>T		intron	N/A	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.2896-582C>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.2686-582C>T		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.2686-582C>T		intron	N/A	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.2686-582C>T		intron	N/A	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000488737.6	TSL:1	n.328-582C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22808 AN: 151934 Hom.: 3262 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.0683

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0975

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.0844 AC: 47186 AN: 559278 Hom.: 4646 Cov.: 0 AF XY: 0.0789 AC XY: 23979 AN XY: 303994

African (AFR) AF: 0.349 AC: 5379 AN: 15402

American (AMR) AF: 0.150 AC: 5364 AN: 35838

Ashkenazi Jewish (ASJ) AF: 0.0872 AC: 1469 AN: 16846

East Asian (EAS) AF: 0.376 AC: 13159 AN: 34952

South Asian (SAS) AF: 0.0597 AC: 3547 AN: 59374

European-Finnish (FIN) AF: 0.0589 AC: 2653 AN: 45074

Middle Eastern (MID) AF: 0.0687 AC: 150 AN: 2184

European-Non Finnish (NFE) AF: 0.0398 AC: 12728 AN: 320018

Other (OTH) AF: 0.0925 AC: 2737 AN: 29590

GnomAD4 genome AF: 0.150 AC: 22846 AN: 152052 Hom.: 3273 Cov.: 32 AF XY: 0.150 AC XY: 11186 AN XY: 74332

African (AFR) AF: 0.349 AC: 14465 AN: 41446

American (AMR) AF: 0.125 AC: 1904 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0975 AC: 338 AN: 3468

East Asian (EAS) AF: 0.373 AC: 1920 AN: 5152

South Asian (SAS) AF: 0.0707 AC: 340 AN: 4812

European-Finnish (FIN) AF: 0.0644 AC: 683 AN: 10598

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0416 AC: 2830 AN: 67988

Other (OTH) AF: 0.135 AC: 284 AN: 2110

Alfa AF: 0.104 Hom.: 226

Bravo AF: 0.168

Asia WGS AF: 0.212 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.78
PhyloP100		-4.2
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: rs4148744; hg19: chr7-87150774;