15-98948832-G-C

Variant names:

• chr15-98948832-G-C
• rs17847195
• NM_000875.5:c.3722+124G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000875.5(IGF1R):​c.3722+124G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000996 in 1,003,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• growth delay due to insulin-like growth factor I resistance

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.3722+124G>C		intron_variant	Intron 20 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.3722+124G>C		intron_variant	Intron 20 of 20		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000649865.1	c.3719+124G>C		intron_variant	Intron 20 of 20			ENSP00000496919.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.96e-7 AC: 1 AN: 1003698 Hom.: 0 AF XY: 0.00000193 AC XY: 1 AN XY: 518406

African (AFR) AF: 0.00 AC: 0 AN: 24912

American (AMR) AF: 0.00 AC: 0 AN: 43146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23228

East Asian (EAS) AF: 0.00 AC: 0 AN: 37532

South Asian (SAS) AF: 0.00 AC: 0 AN: 76482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4688

European-Non Finnish (NFE) AF: 0.00000141 AC: 1 AN: 708864

Other (OTH) AF: 0.00 AC: 0 AN: 45778

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.43
PhyloP100		0.69

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

Other links and lift over

dbSNP: rs17847195; hg19: chr15-99492061;