Variant chr15-98649531-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_000875.5(IGF1R):c.-51T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00068 ( 0 hom. )

Consequence

IGF1R
NM_000875.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.204

Variant links:

Genes affected

IGF1R (HGNC:5465): (insulin like growth factor 1 receptor) This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

IGF1R links:

IRAIN (HGNC:):

IRAIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 15-98649531-T-C is Benign according to our data. Variant chr15-98649531-T-C is described in ClinVar as [Benign]. Clinvar id is 369106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000663 (21/31672) while in subpopulation SAS AF= 0.00712 (9/1264). AF 95% confidence interval is 0.00371. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5 linkuse as main transcript	c.-51T>C		5_prime_UTR_variant	1/21	ENST00000650285.1
IRAIN	NR_126453.2 linkuse as main transcript	n.1257A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1 linkuse as main transcript	c.-51T>C		5_prime_UTR_variant	1/21		NM_000875.5	P4
IGF1R	ENST00000649865.1 linkuse as main transcript	c.-51T>C		5_prime_UTR_variant	1/21			A1

Frequencies

GnomAD3 genomes

AF:

0.000663

AC:

AN:

31678

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000787

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000260

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00712

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000286

Gnomad OTH

AF:

0.00197

GnomAD3 exomes

AF:

0.00224

AC:

AN:

16056

Hom.:

AF XY:

0.00168

AC XY:

AN XY:

8932

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.00140

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00187

Gnomad SAS exome

AF:

0.00438

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000799

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.000677

AC:

AN:

122652

Hom.:

Cov.:

AF XY:

0.000825

AC XY:

AN XY:

64216

show subpopulations

Gnomad4 AFR exome

AF:

0.00804

Gnomad4 AMR exome

AF:

0.00142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00261

Gnomad4 FIN exome

AF:

0.000415

Gnomad4 NFE exome

AF:

0.000218

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.000663

AC:

AN:

31672

Hom.:

Cov.:

AF XY:

0.000642

AC XY:

AN XY:

15572

show subpopulations

Gnomad4 AFR

AF:

0.000787

Gnomad4 AMR

AF:

0.000260

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00712

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000286

Gnomad4 OTH

AF:

0.00195

Alfa

AF:

0.000843

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Growth delay due to insulin-like growth factor I resistance

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

5.4

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over