1-201194178-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

Scores

1
3
13

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.49
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
IGFN1NM_001164586.2 linkc.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
IGFN1ENST00000335211.9 linkc.32C>G p.Pro11Arg missense_variant Exon 3 of 24 5 NM_001164586.2 ENSP00000334714.4 Q86VF2-5
IGFN1ENST00000437879.6 linkn.32C>G non_coding_transcript_exon_variant Exon 3 of 26 1 ENSP00000399041.2 Q86VF2-4
IGFN1ENST00000295591.12 linkc.32C>G p.Pro11Arg missense_variant Exon 3 of 25 5 ENSP00000295591.9 Q86VF2-1

Frequencies

GnomAD3 genomes
AF:
0.00474
AC:
722
AN:
152198
Hom.:
9
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs41313898; hg19: chr1-201163306; API