Genetic Variant IGFN1:p.Pro35Pro (chr1-201194251-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001164586.2(IGFN1):c.105C>T(p.Pro35Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000839 in 1,551,492 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00085 ( 1 hom. )

Consequence

IGFN1
NM_001164586.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.82

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 1-201194251-C-T is Benign according to our data. Variant chr1-201194251-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639747.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.82 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFN1	NM_001164586.2 link	c.105C>T	p.Pro35Pro	synonymous_variant	Exon 3 of 24	ENST00000335211.9	NP_001158058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGFN1	ENST00000335211.9 link	c.105C>T	p.Pro35Pro	synonymous_variant	Exon 3 of 24	5	NM_001164586.2	ENSP00000334714.4	Q86VF2-5
IGFN1	ENST00000437879.6 link	n.105C>T		non_coding_transcript_exon_variant	Exon 3 of 26	1		ENSP00000399041.2	Q86VF2-4
IGFN1	ENST00000295591.12 link	c.105C>T	p.Pro35Pro	synonymous_variant	Exon 3 of 25	5		ENSP00000295591.9	Q86VF2-1

Frequencies

GnomAD3 genomes

AF:

0.000743

AC:

113

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000680

AC:

105

AN:

154464

Hom.:

AF XY:

0.000683

AC XY:

AN XY:

81960

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00294

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000640

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.000921

GnomAD4 exome

AF:

0.000848

AC:

1186

AN:

1399244

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

575

AN XY:

690120

show subpopulations

Gnomad4 AFR exome

AF:

0.000380

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.00346

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.000935

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000755

AC:

115

AN:

152248

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.000684

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IGFN1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

2.4

DANN

Benign

0.75

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over