dbSNP rs17727841: IGF1:c.402+3657C>G (chr12-102415852-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000618.5(IGF1):c.402+3657C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,126 control chromosomes in the GnomAD database, including 1,708 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1708 hom., cov: 31)

Exomes 𝑓: 0.080 ( 0 hom. )

Consequence

IGF1
NM_000618.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.301

Publications

20 publications found

Variant links:

Genes affected

IGF1 (HGNC:5464): (insulin like growth factor 1) The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]

IGF1 links:

LINC02456 (HGNC:53389): (long intergenic non-protein coding RNA 2456)

LINC02456 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5 link	c.402+3657C>G		intron_variant	Intron 3 of 3	ENST00000337514.11	NP_000609.1	P05019-2Q5U743Q59GC5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11 link	c.402+3657C>G		intron_variant	Intron 3 of 3	1	NM_000618.5	ENSP00000337612.7		P05019-2

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20086

AN:

151896

Hom.:

1707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0331

Gnomad AMI

AF:

0.0725

Gnomad AMR

AF:

0.0920

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.153

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.135

GnomAD4 exome

AF:

0.0804

AC:

AN:

112

Hom.:

AF XY:

0.0833

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0682

AC:

AN:

Other (OTH)

AF:

0.100

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.132

AC:

20086

AN:

152014

Hom.:

1708

Cov.:

AF XY:

0.132

AC XY:

9836

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.0331

AC:

1372

AN:

41508

American (AMR)

AF:

0.0919

AC:

1404

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

543

AN:

3470

East Asian (EAS)

AF:

0.167

AC:

858

AN:

5144

South Asian (SAS)

AF:

0.169

AC:

813

AN:

4806

European-Finnish (FIN)

AF:

0.205

AC:

2165

AN:

10546

Middle Eastern (MID)

AF:

0.154

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.184

AC:

12535

AN:

67956

Other (OTH)

AF:

0.135

AC:

285

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

865

1731

2596

3462

4327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<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:

0.161

Hom.:

307

Bravo

AF:

0.118

Asia WGS

AF:

0.147

AC:

509

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

(source)

DANN

Benign

0.68

PhyloP100

-0.30

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over