rs189690117

Variant names:

• chr1-201194177-C-A
• rs189690117
• NM_001164586.2:c.31C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-201194177-C-A
• chr1-201194177-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001164586.2(IGFN1):​c.31C>A​(p.Pro11Thr) 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 1,551,648 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. P11R) has been classified as Likely benign.

• 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: 3.11
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007248342).
• BP6: Variant 1-201194177-C-A is Benign according to our data. Variant chr1-201194177-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3898086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164586.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFN1	NM_001164586.2	MANE Select	c.31C>A	p.Pro11Thr	missense	Exon 3 of 24	NP_001158058.1	Q86VF2-5
	IGFN1	NM_001367841.1		c.31C>A	p.Pro11Thr	missense	Exon 3 of 25	NP_001354770.1	Q86VF2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFN1	ENST00000335211.9	TSL:5 MANE Select	c.31C>A	p.Pro11Thr	missense	Exon 3 of 24	ENSP00000334714.4	Q86VF2-5
	IGFN1	ENST00000437879.6	TSL:1	n.31C>A		non_coding_transcript_exon	Exon 3 of 26	ENSP00000399041.2	Q86VF2-4
	IGFN1	ENST00000295591.12	TSL:5	c.31C>A	p.Pro11Thr	missense	Exon 3 of 25	ENSP00000295591.9	Q86VF2-1

Frequencies

GnomAD3 genomes AF: 0.00475 AC: 723 AN: 152202 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: 0.00706

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00778

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00435 AC: 677 AN: 155692 AF XY: 0.00438

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 FIN exome AF: 0.00893

Gnomad NFE exome AF: 0.00759

Gnomad OTH exome AF: 0.00571

GnomAD4 exome AF: 0.00700 AC: 9802 AN: 1399328 Hom.: 39 Cov.: 31 AF XY: 0.00683 AC XY: 4711 AN XY: 690178

African (AFR) AF: 0.000886 AC: 28 AN: 31596

American (AMR) AF: 0.00151 AC: 54 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.000278 AC: 7 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79234

European-Finnish (FIN) AF: 0.00800 AC: 394 AN: 49270

Middle Eastern (MID) AF: 0.00281 AC: 16 AN: 5694

European-Non Finnish (NFE) AF: 0.00841 AC: 9070 AN: 1078936

Other (OTH) AF: 0.00400 AC: 232 AN: 57986

GnomAD4 genome AF: 0.00475 AC: 723 AN: 152320 Hom.: 9 Cov.: 32 AF XY: 0.00471 AC XY: 351 AN XY: 74478

African (AFR) AF: 0.00135 AC: 56 AN: 41570

American (AMR) AF: 0.00261 AC: 40 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00706 AC: 75 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00778 AC: 529 AN: 68030

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00641 Hom.: 11

Bravo AF: 0.00426

TwinsUK AF: 0.00998 AC: 37

ALSPAC AF: 0.00752 AC: 29

ExAC AF: 0.00254 AC: 70

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Benign	0.059
Eigen_PC	Benign	0.024
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0072	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.1
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.17
Sift	Uncertain	0.019	D
Sift4G	Pathogenic	0.0	D
Vest4		0.19
MVP		0.51
ClinPred		0.028	T
GERP RS		4.5
Varity_R		0.12
gMVP		0.35
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs189690117; hg19: chr1-201163305;