Variant chr15-98962599-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000875.5(IGF1R):c.*5157A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 233,648 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 27 hom., cov: 33)

Exomes 𝑓: 0.018 ( 21 hom. )

Consequence

IGF1R
NM_000875.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.219

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:

SYNM-AS1 (HGNC:55421): (SYNM antisense RNA 1)

SYNM-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 15-98962599-A-G is Benign according to our data. Variant chr15-98962599-A-G is described in ClinVar as [Benign]. Clinvar id is 885318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0183 (2791/152178) while in subpopulation AFR AF= 0.0224 (928/41506). AF 95% confidence interval is 0.0212. There are 27 homozygotes in gnomad4. There are 1343 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5 link	c.*5157A>G		3_prime_UTR_variant	Exon 21 of 21	ENST00000650285.1	NP_000866.1	P08069

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGF1R	ENST00000650285.1 link	c.*5157A>G	3_prime_UTR_variant	Exon 21 of 21		NM_000875.5	ENSP00000497069.1	P08069
IGF1R	ENST00000649865.1 link	c.*5157A>G	3_prime_UTR_variant	Exon 21 of 21			ENSP00000496919.1	C9J5X1
SYNM-AS1	ENST00000559468.1 link	n.348+3390T>C	intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2795

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.0260

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00934

Gnomad FIN

AF:

0.0169

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.0253

GnomAD4 exome

AF:

0.0180

AC:

1470

AN:

81470

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

716

AN XY:

37540

show subpopulations

Gnomad4 AFR exome

AF:

0.0254

Gnomad4 AMR exome

AF:

0.0144

Gnomad4 ASJ exome

AF:

0.0287

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00855

Gnomad4 FIN exome

AF:

0.0144

Gnomad4 NFE exome

AF:

0.0201

Gnomad4 OTH exome

AF:

0.0217

GnomAD4 genome

AF:

0.0183

AC:

2791

AN:

152178

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1343

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0224

Gnomad4 AMR

AF:

0.0155

Gnomad4 ASJ

AF:

0.0260

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00894

Gnomad4 FIN

AF:

0.0169

Gnomad4 NFE

AF:

0.0183

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0201

Hom.:

Bravo

AF:

0.0186

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.0

DANN

Benign

0.61

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over