7-87550882-C-A

Variant names:

• chr7-87550882-C-A
• rs10276036
• NM_001348946.2:c.1000-44G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001348946.2(ABCB1):​c.1000-44G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000054 in 1,110,272 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 66 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.1000-44G>T		intron	N/A	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.1210-44G>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.1000-44G>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.1000-44G>T		intron	N/A	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.1000-44G>T		intron	N/A	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000890305.1		c.1000-44G>T		intron	N/A	ENSP00000560364.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000123 AC: 3 AN: 243236 AF XY: 0.00000757

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000540 AC: 6 AN: 1110272 Hom.: 0 Cov.: 15 AF XY: 0.00000352 AC XY: 2 AN XY: 568462

African (AFR) AF: 0.00 AC: 0 AN: 26432

American (AMR) AF: 0.00 AC: 0 AN: 43946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23924

East Asian (EAS) AF: 0.000158 AC: 6 AN: 38064

South Asian (SAS) AF: 0.00 AC: 0 AN: 78844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5098

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 793358

Other (OTH) AF: 0.00 AC: 0 AN: 48902

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.20
DANN	Benign	0.34
PhyloP100		-0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10276036; hg19: chr7-87180198;