rs1922244

Variant names:

• chr7-87516167-G-A
• rs1922244
• NM_001348946.2:c.3084+342C>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.3084+342C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,018 control chromosomes in the GnomAD database, including 1,459 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 0.11 (1459 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 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.3084+342C>T		intron	N/A	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.3294+342C>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.3084+342C>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.3084+342C>T		intron	N/A	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.3084+342C>T		intron	N/A	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000488737.6	TSL:1	n.726+342C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16272 AN: 151900 Hom.: 1452 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0683

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.0711

Gnomad FIN AF: 0.0636

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0410

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.107 AC: 16298 AN: 152018 Hom.: 1459 Cov.: 32 AF XY: 0.109 AC XY: 8122 AN XY: 74314

African (AFR) AF: 0.201 AC: 8322 AN: 41456

American (AMR) AF: 0.105 AC: 1607 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 330 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1942 AN: 5122

South Asian (SAS) AF: 0.0703 AC: 338 AN: 4806

European-Finnish (FIN) AF: 0.0636 AC: 672 AN: 10566

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0410 AC: 2785 AN: 67994

Other (OTH) AF: 0.105 AC: 223 AN: 2114

Alfa AF: 0.0831 Hom.: 90

Bravo AF: 0.118

Asia WGS AF: 0.205 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.77
PhyloP100		-0.83
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: rs1922244; hg19: chr7-87145483; COSMIC: COSV107221081; COSMIC: COSV107221081;