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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000618.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IGF1	NM_000618.5	MANE Select	c.402+3657C>G	intron	N/A	NP_000609.1	Q5U743
IGF1	NM_001111283.3		c.451+2103C>G	intron	N/A	NP_001104753.1	P05019-4
IGF1	NM_001414007.1		c.402+3657C>G	intron	N/A	NP_001400936.1	Q5U743

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IGF1	ENST00000337514.11	TSL:1 MANE Select	c.402+3657C>G	intron	N/A	ENSP00000337612.7	P05019-2
IGF1	ENST00000424202.6	TSL:1	c.354+3657C>G	intron	N/A	ENSP00000416811.2	P05019-3
IGF1	ENST00000392904.5	TSL:5	c.451+2103C>G	intron	N/A	ENSP00000376637.1	P05019-4

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over