Variant rs13068038 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001135197.2(IHO1):c.1320C>A(p.Asp440Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,614,148 control chromosomes in the GnomAD database, including 8,600 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.094 ( 742 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7858 hom. )

Consequence

IHO1
NM_001135197.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.244

Variant links:

Genes affected

IHO1 (HGNC:27945): (interactor of HORMAD1 1) Predicted to be involved in gamete generation; meiosis I cell cycle process; and regulation of homologous chromosome segregation. Predicted to be active in condensed nuclear chromosome. [provided by Alliance of Genome Resources, Apr 2022]

IHO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013082922).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IHO1	NM_001135197.2 linkuse as main transcript	c.1320C>A	p.Asp440Glu	missense_variant	8/8	ENST00000452691.7	NP_001128669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IHO1	ENST00000452691.7 linkuse as main transcript	c.1320C>A	p.Asp440Glu	missense_variant	8/8	2	NM_001135197.2	ENSP00000407837.2	Q8IYA8-1
IHO1	ENST00000296449.9 linkuse as main transcript	c.1320C>A	p.Asp440Glu	missense_variant	10/10	1		ENSP00000296449.5	Q8IYA8-1
IHO1	ENST00000438782.5 linkuse as main transcript	c.1320C>A	p.Asp440Glu	missense_variant	8/8	5		ENSP00000391788.1	Q8IYA8-1

Frequencies

GnomAD3 genomes

AF:

0.0937

AC:

14252

AN:

152160

Hom.:

742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0839

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0772

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.0350

Gnomad SAS

AF:

0.0600

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.0969

GnomAD3 exomes

AF:

0.0881

AC:

22145

AN:

251272

Hom.:

1096

AF XY:

0.0875

AC XY:

11885

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.0818

Gnomad AMR exome

AF:

0.0513

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.0349

Gnomad SAS exome

AF:

0.0573

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.0966

GnomAD4 exome

AF:

0.101

AC:

148120

AN:

1461870

Hom.:

7858

Cov.:

AF XY:

0.0998

AC XY:

72595

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0817

Gnomad4 AMR exome

AF:

0.0545

Gnomad4 ASJ exome

AF:

0.123

Gnomad4 EAS exome

AF:

0.0404

Gnomad4 SAS exome

AF:

0.0582

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.0957

GnomAD4 genome

AF:

0.0936

AC:

14253

AN:

152278

Hom.:

742

Cov.:

AF XY:

0.0931

AC XY:

6928

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0837

Gnomad4 AMR

AF:

0.0771

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.0353

Gnomad4 SAS

AF:

0.0600

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.0959

Alfa

AF:

0.103

Hom.:

2176

Bravo

AF:

0.0899

TwinsUK

AF:

0.116

AC:

430

ALSPAC

AF:

0.107

AC:

412

ESP6500AA

AF:

0.0872

AC:

384

ESP6500EA

AF:

0.108

AC:

930

ExAC

AF:

0.0884

AC:

10731

Asia WGS

AF:

0.0540

AC:

189

AN:

3478

EpiCase

AF:

0.109

EpiControl

AF:

0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.0070

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.39

.;T;.

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.060

N;N;N

REVEL

Benign

0.056

Sift

Benign

0.12

T;T;T

Sift4G

Uncertain

0.044

D;D;D

Polyphen

0.053

B;B;B

Vest4

0.042

MutPred

0.13

Loss of glycosylation at P445 (P = 0.0368);Loss of glycosylation at P445 (P = 0.0368);Loss of glycosylation at P445 (P = 0.0368);

MPC

0.21

ClinPred

0.0027

GERP RS

-0.45

Varity_R

0.045

gMVP

0.018

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over