rs7174918

Positions:

• chr15-98708127-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.40

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
IGF1R	NM_000875.5	c.640+20C>T		intron_variant		ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.640+20C>T		intron_variant			NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000559925.5	n.640+20C>T		intron_variant		1
IGF1R	ENST00000649865.1	c.640+20C>T		intron_variant				ENSP00000496919.1
IGF1R	ENST00000558355.1	c.277+20C>T		intron_variant		2		ENSP00000453630.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39178 AN: 152032 Hom.: 5760 Cov.: 32

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

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.: 30 AF XY: 0.317 AC XY: 228567 AN XY: 720682

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.: 32 AF XY: 0.258 AC XY: 19208 AN XY: 74374

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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	-0.60
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

Other links and lift over

dbSNP: rs7174918; hg19: chr15-99251356; COSMIC: COSV51269321;