NM_001348946.2:c.2319+1004A>G

Variant names:

• chr7-87540353-T-C
• rs10268314
• NM_001348946.2:c.2319+1004A>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.2319+1004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,274 control chromosomes in the GnomAD database, including 1,395 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 0.13 (1395 hom., cov: 33)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.2319+1004A>G		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.2529+1004A>G		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.2319+1004A>G		intron	N/A	NP_000918.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.2319+1004A>G		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.2319+1004A>G		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000890305.1		c.2319+1004A>G		intron	N/A	ENSP00000560364.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19893 AN: 152156 Hom.: 1387 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0474

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.131 AC: 19935 AN: 152274 Hom.: 1395 Cov.: 33 AF XY: 0.128 AC XY: 9536 AN XY: 74448

African (AFR) AF: 0.171 AC: 7110 AN: 41536

American (AMR) AF: 0.111 AC: 1705 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 522 AN: 3472

East Asian (EAS) AF: 0.0592 AC: 307 AN: 5186

South Asian (SAS) AF: 0.151 AC: 726 AN: 4820

European-Finnish (FIN) AF: 0.0474 AC: 503 AN: 10614

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8543 AN: 68022

Other (OTH) AF: 0.128 AC: 271 AN: 2114

Alfa AF: 0.132 Hom.: 2222

Bravo AF: 0.136

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.78
DANN	Benign	0.73
PhyloP100		-0.96
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: rs10268314; hg19: chr7-87169669;