NM_001348946.2:c.3085-72C>G

Variant names:

• chr7-87515500-G-C
• rs7779562
• NM_001348946.2:c.3085-72C>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.3085-72C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 1,353,484 control chromosomes in the GnomAD database, including 10,762 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 0.16 (3708 hom., cov: 33)
  • Exomes 𝑓: 0.069 (7054 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 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.3085-72C>G		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.3295-72C>G		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.3085-72C>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.3085-72C>G		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.3085-72C>G		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000488737.6	TSL:1	n.727-72C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24249 AN: 152114 Hom.: 3693 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.0722

Gnomad FIN AF: 0.0642

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0419

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.0689 AC: 82818 AN: 1201252 Hom.: 7054 AF XY: 0.0668 AC XY: 40554 AN XY: 606898

African (AFR) AF: 0.399 AC: 11526 AN: 28874

American (AMR) AF: 0.156 AC: 6241 AN: 40098

Ashkenazi Jewish (ASJ) AF: 0.0892 AC: 2157 AN: 24192

East Asian (EAS) AF: 0.382 AC: 14435 AN: 37836

South Asian (SAS) AF: 0.0617 AC: 4812 AN: 77976

European-Finnish (FIN) AF: 0.0684 AC: 3515 AN: 51416

Middle Eastern (MID) AF: 0.0690 AC: 363 AN: 5264

European-Non Finnish (NFE) AF: 0.0395 AC: 34895 AN: 883952

Other (OTH) AF: 0.0944 AC: 4874 AN: 51644

GnomAD4 genome AF: 0.160 AC: 24295 AN: 152232 Hom.: 3708 Cov.: 33 AF XY: 0.159 AC XY: 11843 AN XY: 74444

African (AFR) AF: 0.380 AC: 15777 AN: 41504

American (AMR) AF: 0.127 AC: 1952 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3470

East Asian (EAS) AF: 0.381 AC: 1974 AN: 5176

South Asian (SAS) AF: 0.0714 AC: 344 AN: 4816

European-Finnish (FIN) AF: 0.0642 AC: 680 AN: 10600

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0419 AC: 2851 AN: 68032

Other (OTH) AF: 0.140 AC: 297 AN: 2116

Alfa AF: 0.0246 Hom.: 17

Bravo AF: 0.178

Asia WGS AF: 0.216 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.42
PhyloP100		-0.18
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: rs7779562; hg19: chr7-87144816; COSMIC: COSV55953102; COSMIC: COSV55953102;