1-201194178-C-G

Variant names:

• chr1-201194178-C-G
• rs41313898
• NM_001164586.2:c.32C>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001164586.2(IGFN1):​c.32C>G​(p.Pro11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,551,644 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P11S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0047 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0070 (39 hom.)
• Consequence: IGFN1 NM_001164586.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.49

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007978797).
• BP6: Variant 1-201194178-C-G is Benign according to our data. Variant chr1-201194178-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3898087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFN1	NM_001164586.2	c.32C>G	p.Pro11Arg	missense_variant	Exon 3 of 24	ENST00000335211.9	NP_001158058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFN1	ENST00000335211.9	c.32C>G	p.Pro11Arg	missense_variant	Exon 3 of 24	5	NM_001164586.2	ENSP00000334714.4
IGFN1	ENST00000437879.6	n.32C>G		non_coding_transcript_exon_variant	Exon 3 of 26	1		ENSP00000399041.2
IGFN1	ENST00000295591.12	c.32C>G	p.Pro11Arg	missense_variant	Exon 3 of 25	5		ENSP00000295591.9

Frequencies

GnomAD3 genomes AF: 0.00474 AC: 722 AN: 152198 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00697

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00778

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00435 AC: 677 AN: 155666 Hom.: 1 AF XY: 0.00439 AC XY: 362 AN XY: 82540

Gnomad AFR exome AF: 0.000885

Gnomad AMR exome AF: 0.00166

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000439

Gnomad FIN exome AF: 0.00894

Gnomad NFE exome AF: 0.00759

Gnomad OTH exome AF: 0.00571

GnomAD4 exome AF: 0.00701 AC: 9805 AN: 1399328 Hom.: 39 Cov.: 31 AF XY: 0.00683 AC XY: 4712 AN XY: 690170

Gnomad4 AFR exome AF: 0.000886

Gnomad4 AMR exome AF: 0.00151

Gnomad4 ASJ exome AF: 0.000278

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000252

Gnomad4 FIN exome AF: 0.00800

Gnomad4 NFE exome AF: 0.00841

Gnomad4 OTH exome AF: 0.00400

GnomAD4 genome AF: 0.00474 AC: 722 AN: 152316 Hom.: 9 Cov.: 32 AF XY: 0.00470 AC XY: 350 AN XY: 74476

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00697

Gnomad4 NFE AF: 0.00778

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00231 Hom.: 1

Bravo AF: 0.00426

TwinsUK AF: 0.00998 AC: 37

ALSPAC AF: 0.00752 AC: 29

ExAC AF: 0.00255 AC: 70

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IGFN1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.040	.;T
Eigen	Benign	-0.053
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.59	T;T
MetaRNN	Benign	0.0080	T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.25
Sift	Uncertain	0.025	D;.
Sift4G	Pathogenic	0.0	D;D
Vest4		0.17
MVP		0.54
ClinPred		0.028	T
GERP RS		3.6
Varity_R		0.044
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41313898; hg19: chr1-201163306;