Genetic Variant IGF1:c.220+12774T>C (chr12-102462869-A-G) – 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.220+12774T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,102 control chromosomes in the GnomAD database, including 5,485 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 0.26 ( 5485 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IGF1
NM_000618.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.304

Publications

12 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=-0.52).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 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
IGF1	NM_000618.5	MANE Select	c.220+12774T>C	intron	N/A	NP_000609.1
IGF1	NM_001111285.3		c.220+12774T>C	intron	N/A	NP_001104755.1
IGF1	NM_001414005.1		c.220+12774T>C	intron	N/A	NP_001400934.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IGF1	ENST00000337514.11	TSL:1 MANE Select	c.220+12774T>C	intron	N/A	ENSP00000337612.7
IGF1	ENST00000307046.8	TSL:1	c.220+12774T>C	intron	N/A	ENSP00000302665.8
IGF1	ENST00000424202.6	TSL:1	c.172+12774T>C	intron	N/A	ENSP00000416811.2

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39948

AN:

151984

Hom.:

5461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.244

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.263

AC:

40016

AN:

152102

Hom.:

5485

Cov.:

AF XY:

0.265

AC XY:

19706

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.293

AC:

12156

AN:

41504

American (AMR)

AF:

0.205

AC:

3132

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

706

AN:

3468

East Asian (EAS)

AF:

0.434

AC:

2248

AN:

5174

South Asian (SAS)

AF:

0.283

AC:

1363

AN:

4820

European-Finnish (FIN)

AF:

0.334

AC:

3522

AN:

10548

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16228

AN:

67974

Other (OTH)

AF:

0.250

AC:

529

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1485

2971

4456

5942

7427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.256

Hom.:

1880

Bravo

AF:

0.256

Asia WGS

AF:

0.402

AC:

1397

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.71

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