rs4915221

Variant names:

• chr1-201197255-G-A
• rs4915221
• NM_001164586.2:c.305G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-201197255-G-A
• chr1-201197255-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894
• Publications: 25 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IGFN1	NM_001164586.2	c.305G>A	p.Arg102His	missense_variant	Exon 5 of 24	ENST00000335211.9	NP_001158058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFN1	ENST00000335211.9	c.305G>A	p.Arg102His	missense_variant	Exon 5 of 24	5	NM_001164586.2	ENSP00000334714.4
IGFN1	ENST00000437879.6	n.305G>A		non_coding_transcript_exon_variant	Exon 5 of 26	1		ENSP00000399041.2
IGFN1	ENST00000295591.12	c.305G>A	p.Arg102His	missense_variant	Exon 5 of 25	5		ENSP00000295591.9

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97977 AN: 152062 Hom.: 32425 Cov.: 34

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

GnomAD2 exomes AF: 0.635 AC: 99125 AN: 156220 AF XY: 0.639

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 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.: 39 AF XY: 0.591 AC XY: 407352 AN XY: 689248

African (AFR) AF: 0.791 AC: 24986 AN: 31582

American (AMR) AF: 0.620 AC: 22125 AN: 35688

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 14756 AN: 25160

East Asian (EAS) AF: 0.835 AC: 29850 AN: 35730

South Asian (SAS) AF: 0.748 AC: 59206 AN: 79194

European-Finnish (FIN) AF: 0.603 AC: 29667 AN: 49196

Middle Eastern (MID) AF: 0.556 AC: 3169 AN: 5696

European-Non Finnish (NFE) AF: 0.558 AC: 601359 AN: 1077314

Other (OTH) AF: 0.618 AC: 35812 AN: 57936

GnomAD4 genome AF: 0.644 AC: 98056 AN: 152180 Hom.: 32452 Cov.: 34 AF XY: 0.651 AC XY: 48456 AN XY: 74412

African (AFR) AF: 0.778 AC: 32297 AN: 41530

American (AMR) AF: 0.611 AC: 9331 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2059 AN: 3472

East Asian (EAS) AF: 0.847 AC: 4386 AN: 5176

South Asian (SAS) AF: 0.761 AC: 3675 AN: 4830

European-Finnish (FIN) AF: 0.619 AC: 6546 AN: 10582

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37898 AN: 67986

Other (OTH) AF: 0.614 AC: 1300 AN: 2116

Alfa AF: 0.584 Hom.: 118614

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
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.63	T;T
MetaRNN	Benign	0.0000055	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M
PhyloP100		0.89
PrimateAI	Benign	0.24	T
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	T
GERP RS		3.2
Varity_R		0.049
gMVP		0.41
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4915221; hg19: chr1-201166383; COSMIC: COSV55168830;