Genetic Variant ENSG00000276490:n.932-13158C>T (chr10-94761900-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The ENST00000464755.1(ENSG00000276490):n.932-13158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000464755.1 is not a MANE Select or MANE Plus Clinical transcript for ENSG00000276490; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.2 (AC=30,385) in the gnomAD database across 151,940 control chromosomes, including 3,261 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.217. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (★★★★).

Frequency

Genomes: 𝑓 0.20 ( 3261 hom., cov: 32)

Consequence

ENSG00000276490
ENST00000464755.1 intron

Scores

Clinical Significance

drug response practice guideline B:1O:3

Conservation

PhyloP100: -0.799

Publications

563 publications found

Variant links:

Genes affected

ENSG00000276490 (HGNC:):

ENSG00000276490 links:

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new If you want to explore the variant's impact on the transcript ENST00000464755.1, 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.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.2173 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000464755.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000276490	ENST00000464755.1	TSL:2	n.932-13158C>T		intron	N/A	ENSP00000483243.1	A0A087X0B3

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30383

AN:

151824

Hom.:

3260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.00945

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.200

AC:

30385

AN:

151940

Hom.:

3261

Cov.:

AF XY:

0.197

AC XY:

14601

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.221

AC:

9161

AN:

41430

American (AMR)

AF:

0.133

AC:

2031

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

740

AN:

3468

East Asian (EAS)

AF:

0.00947

AC:

AN:

5174

South Asian (SAS)

AF:

0.163

AC:

785

AN:

4820

European-Finnish (FIN)

AF:

0.185

AC:

1943

AN:

10506

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.220

AC:

14949

AN:

67948

Other (OTH)

AF:

0.198

AC:

418

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1203

2405

3608

4810

6013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.212

Hom.:

1020

Bravo

AF:

0.196

Asia WGS

AF:

0.0850

AC:

297

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0104

AC:

1280

AN:

122760

Turkish Variome

AF:

0.208

AC:

321

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.00647

AC:

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.195

AC:

456

AN:

2342

Hom.:

ClinVar

ClinVar submissions

Significance:drug response

Revision:practice guideline

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Clopidogrel response (1)

CYP2C19: increased function (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.27

(source)

DANN

Benign

0.50

PhyloP100

-0.80

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

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over