Genetic Variant NM_001164586.2:c.105C>T (chr1-201194251-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_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

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

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 VariationId is 2639747.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

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

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.105C>T	p.Pro35Pro	synonymous	Exon 3 of 24	NP_001158058.1	Q86VF2-5
	IGFN1	NM_001367841.1		c.105C>T	p.Pro35Pro	synonymous	Exon 3 of 25	NP_001354770.1	Q86VF2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGFN1	ENST00000335211.9	TSL:5 MANE Select	c.105C>T	p.Pro35Pro	synonymous	Exon 3 of 24	ENSP00000334714.4	Q86VF2-5
IGFN1	ENST00000437879.6	TSL:1	n.105C>T		non_coding_transcript_exon	Exon 3 of 26	ENSP00000399041.2	Q86VF2-4
IGFN1	ENST00000295591.12	TSL:5	c.105C>T	p.Pro35Pro	synonymous	Exon 3 of 25	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

GnomAD2 exomes

AF:

0.000680

AC:

105

AN:

154464

AF XY:

0.000683

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 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

African (AFR)

AF:

0.000380

AC:

AN:

31596

American (AMR)

AF:

0.000168

AC:

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

25174

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.00

AC:

AN:

79230

European-Finnish (FIN)

AF:

0.0000203

AC:

AN:

49252

Middle Eastern (MID)

AF:

0.00194

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.000935

AC:

1009

AN:

1078904

Other (OTH)

AF:

0.00103

AC:

AN:

57982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

117

175

234

292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000755

AC:

115

AN:

152248

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41554

American (AMR)

AF:

0.000457

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00110

AC:

AN:

68004

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.000684

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

2.4

(source)

DANN

Benign

0.75

PhyloP100

-1.8

Mutation Taster

=295/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over