Variant rs7174918 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000875.5(IGF1R):c.640+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,598,980 control chromosomes in the GnomAD database, including 78,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 5767 hom., cov: 32)

Exomes 𝑓: 0.31 ( 72816 hom. )

Consequence

IGF1R
NM_000875.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.40

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:

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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=-0.6).

BP6

Variant 15-98708127-C-T is Benign according to our data. Variant chr15-98708127-C-T is described in ClinVar as [Benign]. Clinvar id is 1622379.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-98708127-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5 linkuse as main transcript	c.640+20C>T		intron_variant		ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
IGF1R	ENST00000650285.1 linkuse as main transcript	c.640+20C>T	intron_variant		NM_000875.5	P4
IGF1R	ENST00000559925.5 linkuse as main transcript	n.640+20C>T	intron_variant, non_coding_transcript_variant	1
IGF1R	ENST00000558355.1 linkuse as main transcript	c.277+20C>T	intron_variant	2
IGF1R	ENST00000649865.1 linkuse as main transcript	c.640+20C>T	intron_variant			A1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39178

AN:

152032

Hom.:

5760

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.223

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.275

GnomAD3 exomes

AF:

0.291

AC:

70650

AN:

242864

Hom.:

10884

AF XY:

0.302

AC XY:

39934

AN XY:

132076

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.224

Gnomad ASJ exome

AF:

0.338

Gnomad EAS exome

AF:

0.229

Gnomad SAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.280

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.314

AC:

453804

AN:

1446830

Hom.:

72816

Cov.:

AF XY:

0.317

AC XY:

228567

AN XY:

720682

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.229

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.216

Gnomad4 SAS exome

AF:

0.361

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.324

Gnomad4 OTH exome

AF:

0.312

GnomAD4 genome

AF:

0.258

AC:

39190

AN:

152150

Hom.:

5767

Cov.:

AF XY:

0.258

AC XY:

19208

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.345

Gnomad4 EAS

AF:

0.223

Gnomad4 SAS

AF:

0.344

Gnomad4 FIN

AF:

0.261

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.283

Hom.:

1776

Bravo

AF:

0.248

Asia WGS

AF:

0.305

AC:

1059

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.1

DANN

Benign

0.84

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