chr15-98649525-CTTTTTTTTT-C

Position:

• chr15-98649525-CTTTTTTTTT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000875.5(IGF1R):​c.-41_-33del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 715,492 control chromosomes in the GnomAD database, including 17,858 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (8308 hom., cov: 0)
  • Exomes 𝑓: 0.36 (9550 hom.)
• Consequence: IGF1R NM_000875.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.58

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]

IRAIN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 15-98649525-CTTTTTTTTT-C is Benign according to our data. Variant chr15-98649525-CTTTTTTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 369105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.-41_-33del		5_prime_UTR_variant	1/21	ENST00000650285.1	NP_000866.1
IRAIN	NR_126453.2	n.1254_1262del		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.-41_-33del		5_prime_UTR_variant	1/21		NM_000875.5	ENSP00000497069	P4
IGF1R	ENST00000649865.1	c.-41_-33del		5_prime_UTR_variant	1/21			ENSP00000496919	A1
IGF1R	ENST00000559925.5			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 44851 AN: 124932 Hom.: 8308 Cov.: 0

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.360 AC: 212862 AN: 590552 Hom.: 9550 AF XY: 0.357 AC XY: 112240 AN XY: 314618

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.304

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.384

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.359 AC: 44841 AN: 124940 Hom.: 8308 Cov.: 0 AF XY: 0.366 AC XY: 21874 AN XY: 59692

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.348

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Growth delay due to insulin-like growth factor I resistance Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Nov 16, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs544674838; hg19: chr15-99192754;