7-87515500-G-A

Position:

• chr7-87515500-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001348946.2(ABCB1):​c.3085-72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,353,974 control chromosomes in the GnomAD database, including 1 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 0.00097 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (1 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS2: High AC in GnomAd4 at 148 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.3085-72C>T		intron_variant		ENST00000622132.5	NP_001335875.1
ABCB1	NM_000927.5	c.3085-72C>T		intron_variant			NP_000918.2
ABCB1	NM_001348944.2	c.3085-72C>T		intron_variant			NP_001335873.1
ABCB1	NM_001348945.2	c.3295-72C>T		intron_variant			NP_001335874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.3085-72C>T		intron_variant		1	NM_001348946.2	ENSP00000478255	P1

Frequencies

GnomAD3 genomes AF: 0.000973 AC: 148 AN: 152136 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000719

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00137 AC: 1646 AN: 1201720 Hom.: 1 AF XY: 0.00137 AC XY: 830 AN XY: 607128

Gnomad4 AFR exome AF: 0.000138

Gnomad4 AMR exome AF: 0.000798

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000264

Gnomad4 SAS exome AF: 0.0000385

Gnomad4 FIN exome AF: 0.00132

Gnomad4 NFE exome AF: 0.00169

Gnomad4 OTH exome AF: 0.000910

GnomAD4 genome AF: 0.000972 AC: 148 AN: 152254 Hom.: 0 Cov.: 33 AF XY: 0.000900 AC XY: 67 AN XY: 74454

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000718

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000187 Hom.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs7779562; hg19: chr7-87144816;