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

Variant names:

• chr7-87515500-G-A
• rs7779562
• NM_001348946.2:c.3085-72C>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.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
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS2: High AC in GnomAd4 at 148 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.3085-72C>T		intron	N/A	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.3295-72C>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.3085-72C>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.3085-72C>T		intron	N/A	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.3085-72C>T		intron	N/A	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000488737.6	TSL:1	n.727-72C>T		intron	N/A

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

African (AFR) AF: 0.000138 AC: 4 AN: 28912

American (AMR) AF: 0.000798 AC: 32 AN: 40114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24196

East Asian (EAS) AF: 0.0000264 AC: 1 AN: 37868

South Asian (SAS) AF: 0.0000385 AC: 3 AN: 77996

European-Finnish (FIN) AF: 0.00132 AC: 68 AN: 51430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5266

European-Non Finnish (NFE) AF: 0.00169 AC: 1491 AN: 884270

Other (OTH) AF: 0.000910 AC: 47 AN: 51668

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

African (AFR) AF: 0.000265 AC: 11 AN: 41520

American (AMR) AF: 0.000718 AC: 11 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00160 AC: 109 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000187 Hom.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.25
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

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;