7-87509195-G-A

Variant names:

• chr7-87509195-G-A
• rs2235048
• NM_001348946.2:c.3489+80C>T

Variant summary

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

The ENST00000622132.5(ABCB1):​c.3489+80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,435,846 control chromosomes in the GnomAD database, including 174,173 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 0.57 (26515 hom., cov: 31)
  • Exomes 𝑓: 0.47 (147658 hom.)
• Consequence: ABCB1 ENST00000622132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833
• Publications: 41 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 (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000622132.5. 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.3489+80C>T		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.3699+80C>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.3489+80C>T		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.3489+80C>T		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.3489+80C>T		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000488737.6	TSL:1	n.1131+80C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86593 AN: 151916 Hom.: 26459 Cov.: 31

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.596

GnomAD4 exome AF: 0.472 AC: 605993 AN: 1283812 Hom.: 147658 AF XY: 0.468 AC XY: 303111 AN XY: 647248

African (AFR) AF: 0.817 AC: 24344 AN: 29792

American (AMR) AF: 0.545 AC: 23942 AN: 43946

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 16083 AN: 25002

East Asian (EAS) AF: 0.600 AC: 23240 AN: 38730

South Asian (SAS) AF: 0.392 AC: 32403 AN: 82678

European-Finnish (FIN) AF: 0.391 AC: 19426 AN: 49692

Middle Eastern (MID) AF: 0.542 AC: 2813 AN: 5194

European-Non Finnish (NFE) AF: 0.457 AC: 436066 AN: 954184

Other (OTH) AF: 0.507 AC: 27676 AN: 54594

GnomAD4 genome AF: 0.570 AC: 86711 AN: 152034 Hom.: 26515 Cov.: 31 AF XY: 0.567 AC XY: 42128 AN XY: 74302

African (AFR) AF: 0.797 AC: 33043 AN: 41468

American (AMR) AF: 0.564 AC: 8614 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2241 AN: 3468

East Asian (EAS) AF: 0.616 AC: 3185 AN: 5168

South Asian (SAS) AF: 0.410 AC: 1971 AN: 4810

European-Finnish (FIN) AF: 0.380 AC: 4013 AN: 10564

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31714 AN: 67968

Other (OTH) AF: 0.595 AC: 1255 AN: 2110

Alfa AF: 0.513 Hom.: 49202

Bravo AF: 0.597

Asia WGS AF: 0.515 AC: 1791 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	3.8
DANN	Benign	0.36
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: rs2235048; hg19: chr7-87138511;