rs13068038

chr3-49256817-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 12/18 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

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]

ACMG classification

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	UniProt
IHO1	NM_001135197.2	c.1320C>A	p.Asp440Glu	missense_variant	8/8	ENST00000452691.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IHO1	ENST00000452691.7	c.1320C>A	p.Asp440Glu	missense_variant	8/8	2	NM_001135197.2	P1
IHO1	ENST00000296449.9	c.1320C>A	p.Asp440Glu	missense_variant	10/10	1		P1
IHO1	ENST00000438782.5	c.1320C>A	p.Asp440Glu	missense_variant	8/8	5		P1

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14252 AN: 152160 Hom.: 742 Cov.: 32

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

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.: 32 AF XY: 0.0998 AC XY: 72595 AN XY: 727238

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.: 32 AF XY: 0.0931 AC XY: 6928 AN XY: 74450

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	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	11
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	N
MetaRNN	Benign	0.0013	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.27	T
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	T
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

Other links and lift over

dbSNP: rs13068038; hg19: chr3-49294250; COSMIC: COSV56506907; COSMIC: COSV56506907;