Variant 20-13270741-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_080826.2(ISM1):c.376C>G(p.Gln126Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000487 in 1,613,250 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00074 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00046 ( 8 hom. )

Consequence

ISM1
NM_080826.2 missense, splice_region

Scores

Splicing: ADA: 0.9059

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.14

Variant links:

Genes affected

ISM1 (HGNC:16213): (isthmin 1) Predicted to be involved in negative regulation of angiogenesis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ISM1 links:

TASP1 (HGNC:):

TASP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010455579).

BP6

Variant 20-13270741-C-G is Benign according to our data. Variant chr20-13270741-C-G is described in ClinVar as [Benign]. Clinvar id is 3044524.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000742 (113/152312) while in subpopulation EAS AF= 0.0195 (101/5186). AF 95% confidence interval is 0.0164. There are 3 homozygotes in gnomad4. There are 60 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISM1	NM_080826.2 linkuse as main transcript	c.376C>G	p.Gln126Glu	missense_variant, splice_region_variant	2/6	ENST00000262487.5	NP_543016.1	B1AKI9
ISM1	XM_017027680.2 linkuse as main transcript	c.376C>G	p.Gln126Glu	missense_variant, splice_region_variant	2/7		XP_016883169.1
TASP1	XR_001754319.3 linkuse as main transcript	n.1369+45229G>C		intron_variant
TASP1	XR_007067463.1 linkuse as main transcript	n.1370-4559G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISM1	ENST00000262487.5 linkuse as main transcript	c.376C>G	p.Gln126Glu	missense_variant, splice_region_variant	2/6	5	NM_080826.2	ENSP00000262487.3		B1AKI9

Frequencies

GnomAD3 genomes

AF:

0.000756

AC:

115

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0196

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00155

AC:

383

AN:

247850

Hom.:

AF XY:

0.00141

AC XY:

190

AN XY:

134430

show subpopulations

Gnomad AFR exome

AF:

0.0000650

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0210

Gnomad SAS exome

AF:

0.0000988

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000460

AC:

672

AN:

1460938

Hom.:

Cov.:

AF XY:

0.000494

AC XY:

359

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0156

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000742

AC:

113

AN:

152312

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0195

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000687

Hom.:

Bravo

AF:

0.000986

ExAC

AF:

0.00147

AC:

178

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ISM1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.0

REVEL

Benign

0.19

Sift

Benign

0.084

Sift4G

Benign

0.11

Polyphen

0.98

Vest4

0.85

MVP

0.63

MPC

0.042

ClinPred

0.068

GERP RS

5.7

Varity_R

0.34

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.91

dbscSNV1_RF

Benign

0.61

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over