Genetic Variant NM_001348946.2:c.3435T>A (chr7-87509329-A-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is . The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001348946.2(ABCB1):c.3435T>A(p.Ile1145Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I1145I) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Consequence

ABCB1
NM_001348946.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.52

Publications

3153 publications found

Variant links:

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]

ABCB1 Gene-Disease associations (from GenCC):

inflammatory bowel disease 13
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ABCB1 links:

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new If you want to explore the variant's impact on the transcript NM_001348946.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP7

Synonymous conserved (PhyloP=-2.52 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCB1	NM_001348946.2	MANE Select	c.3435T>A	p.Ile1145Ile	synonymous	Exon 26 of 28	NP_001335875.1	P08183-1
ABCB1	NM_001348945.2		c.3645T>A	p.Ile1215Ile	synonymous	Exon 30 of 32	NP_001335874.1
ABCB1	NM_000927.5		c.3435T>A	p.Ile1145Ile	synonymous	Exon 27 of 29	NP_000918.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.3435T>A	p.Ile1145Ile	synonymous	Exon 26 of 28	ENSP00000478255.1	P08183-1
ABCB1	ENST00000265724.8	TSL:1	c.3435T>A	p.Ile1145Ile	synonymous	Exon 27 of 29	ENSP00000265724.3	P08183-1
ABCB1	ENST00000488737.6	TSL:1	n.1077T>A		non_coding_transcript_exon	Exon 7 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.021

(source)

DANN

Benign

0.55

PhyloP100

-2.5

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over