Variant rs4915221 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001164586.2(IGFN1):c.305G>A(p.Arg102His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,549,676 control chromosomes in the GnomAD database, including 277,516 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.64 ( 32452 hom., cov: 34)

Exomes 𝑓: 0.59 ( 245064 hom. )

Consequence

IGFN1
NM_001164586.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.894

Variant links:

Genes affected

IGFN1 (HGNC:24607): (immunoglobulin like and fibronectin type III domain containing 1) Predicted to be involved in homophilic cell adhesion via plasma membrane adhesion molecules; retina layer formation; and synapse assembly. Predicted to be located in Z disc and nucleus. Predicted to be active in synapse. [provided by Alliance of Genome Resources, Apr 2022]

IGFN1 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=5.5280852E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFN1	NM_001164586.2 linkuse as main transcript	c.305G>A	p.Arg102His	missense_variant	5/24	ENST00000335211.9	NP_001158058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFN1	ENST00000335211.9 linkuse as main transcript	c.305G>A	p.Arg102His	missense_variant	5/24	5	NM_001164586.2	ENSP00000334714	P2	Q86VF2-5
IGFN1	ENST00000437879.6 linkuse as main transcript	c.305G>A	p.Arg102His	missense_variant, NMD_transcript_variant	5/26	1		ENSP00000399041		Q86VF2-4
IGFN1	ENST00000295591.12 linkuse as main transcript	c.305G>A	p.Arg102His	missense_variant	5/25	5		ENSP00000295591	A2	Q86VF2-1

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97977

AN:

152062

Hom.:

32425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.611

Gnomad ASJ

AF:

0.593

Gnomad EAS

AF:

0.846

Gnomad SAS

AF:

0.761

Gnomad FIN

AF:

0.619

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.557

Gnomad OTH

AF:

0.611

GnomAD3 exomes

AF:

0.635

AC:

99125

AN:

156220

Hom.:

32287

AF XY:

0.639

AC XY:

52870

AN XY:

82798

show subpopulations

Gnomad AFR exome

AF:

0.785

Gnomad AMR exome

AF:

0.627

Gnomad ASJ exome

AF:

0.586

Gnomad EAS exome

AF:

0.836

Gnomad SAS exome

AF:

0.746

Gnomad FIN exome

AF:

0.605

Gnomad NFE exome

AF:

0.557

Gnomad OTH exome

AF:

0.597

GnomAD4 exome

AF:

0.587

AC:

820930

AN:

1397496

Hom.:

245064

Cov.:

AF XY:

0.591

AC XY:

407352

AN XY:

689248

show subpopulations

Gnomad4 AFR exome

AF:

0.791

Gnomad4 AMR exome

AF:

0.620

Gnomad4 ASJ exome

AF:

0.586

Gnomad4 EAS exome

AF:

0.835

Gnomad4 SAS exome

AF:

0.748

Gnomad4 FIN exome

AF:

0.603

Gnomad4 NFE exome

AF:

0.558

Gnomad4 OTH exome

AF:

0.618

GnomAD4 genome

AF:

0.644

AC:

98056

AN:

152180

Hom.:

32452

Cov.:

AF XY:

0.651

AC XY:

48456

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.778

Gnomad4 AMR

AF:

0.611

Gnomad4 ASJ

AF:

0.593

Gnomad4 EAS

AF:

0.847

Gnomad4 SAS

AF:

0.761

Gnomad4 FIN

AF:

0.619

Gnomad4 NFE

AF:

0.557

Gnomad4 OTH

AF:

0.614

Alfa

AF:

0.573

Hom.:

61782

Bravo

AF:

0.647

TwinsUK

AF:

0.572

AC:

2122

ALSPAC

AF:

0.555

AC:

2138

ESP6500AA

AF:

0.770

AC:

1065

ESP6500EA

AF:

0.569

AC:

1812

ExAC

AF:

0.639

AC:

15832

Asia WGS

AF:

0.801

AC:

2781

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

.;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0000055

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

0.67

P;P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.20

Sift

Benign

0.069

T;.

Sift4G

Benign

0.21

T;T

Vest4

0.15

ClinPred

0.014

GERP RS

3.2

Varity_R

0.049

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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