Variant rs34364279 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_000875.5(IGF1R):c.3918C>T(p.Asp1306Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000257 in 1,614,142 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 2 hom. )

Consequence

IGF1R
NM_000875.5 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.81

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:

IGF1R (HGNC:):

IGF1R links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 15-98957256-C-T is Benign according to our data. Variant chr15-98957256-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 499748.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}. Variant chr15-98957256-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.81 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00123 (188/152356) while in subpopulation AFR AF= 0.00418 (174/41590). AF 95% confidence interval is 0.00368. There are 1 homozygotes in gnomad4. There are 90 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1R	NM_000875.5 linkuse as main transcript	c.3918C>T	p.Asp1306Asp	synonymous_variant	21/21	ENST00000650285.1	NP_000866.1	P08069

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGF1R	ENST00000650285.1 linkuse as main transcript	c.3918C>T	p.Asp1306Asp	synonymous_variant	21/21		NM_000875.5	ENSP00000497069.1	P08069
IGF1R	ENST00000649865.1 linkuse as main transcript	c.3915C>T	p.Asp1305Asp	synonymous_variant	21/21			ENSP00000496919.1	C9J5X1
IGF1R	ENST00000558751.1 linkuse as main transcript	n.512C>T		non_coding_transcript_exon_variant	2/2	4
SYNM-AS1	ENST00000559468.1 linkuse as main transcript	n.349-2868G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

191

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00427

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000407

AC:

102

AN:

250842

Hom.:

AF XY:

0.000346

AC XY:

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.00452

Gnomad AMR exome

AF:

0.000753

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000155

AC:

227

AN:

1461786

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

100

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00487

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.00123

AC:

188

AN:

152356

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00418

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000805

Hom.:

Bravo

AF:

0.00168

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 13, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 23, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.88

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