Genetic Variant IGF1:c.64-23C>A (chr12-102475822-G-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_000618.5(IGF1):c.64-23C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,602,894 control chromosomes in the GnomAD database, including 759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.032 ( 99 hom., cov: 32)

Exomes 𝑓: 0.028 ( 660 hom. )

Consequence

IGF1
NM_000618.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.11

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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.2).

BP6

Variant 12-102475822-G-T is Benign according to our data. Variant chr12-102475822-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0325 (4943/152216) while in subpopulation AFR AF= 0.0402 (1668/41530). AF 95% confidence interval is 0.0386. There are 99 homozygotes in gnomad4. There are 2407 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 99 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5 link	c.64-23C>A		intron_variant	Intron 1 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.64-23C>A		intron_variant	Intron 1 of 3	1	NM_000618.5	ENSP00000337612.7		P05019-2

Frequencies

GnomAD3 genomes

AF:

0.0325

AC:

4936

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0401

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00540

Gnomad FIN

AF:

0.0392

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0318

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0248

AC:

5677

AN:

229324

Hom.:

AF XY:

0.0243

AC XY:

3003

AN XY:

123552

show subpopulations

Gnomad AFR exome

AF:

0.0419

Gnomad AMR exome

AF:

0.0216

Gnomad ASJ exome

AF:

0.0197

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00434

Gnomad FIN exome

AF:

0.0431

Gnomad NFE exome

AF:

0.0298

Gnomad OTH exome

AF:

0.0272

GnomAD4 exome

AF:

0.0285

AC:

41291

AN:

1450678

Hom.:

660

Cov.:

AF XY:

0.0277

AC XY:

19955

AN XY:

720598

show subpopulations

Gnomad4 AFR exome

AF:

0.0386

Gnomad4 AMR exome

AF:

0.0230

Gnomad4 ASJ exome

AF:

0.0220

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00467

Gnomad4 FIN exome

AF:

0.0445

Gnomad4 NFE exome

AF:

0.0308

Gnomad4 OTH exome

AF:

0.0267

GnomAD4 genome

AF:

0.0325

AC:

4943

AN:

152216

Hom.:

Cov.:

AF XY:

0.0323

AC XY:

2407

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0402

Gnomad4 AMR

AF:

0.0285

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00561

Gnomad4 FIN

AF:

0.0392

Gnomad4 NFE

AF:

0.0318

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0300

Hom.:

Bravo

AF:

0.0324

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over