chr15-98927092-G-C

Variant names:

• chr15-98927092-G-C
• rs1546714
• NM_000875.5:c.2782+2408G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000875.5(IGF1R):​c.2782+2408G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 152,304 control chromosomes in the GnomAD database, including 72,245 homozygotes. 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: 𝑓 0.97 (72245 hom., cov: 32)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000875.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	NM_000875.5	MANE Select	c.2782+2408G>C		intron	N/A	NP_000866.1
	IGF1R	NM_001291858.2		c.2782+2408G>C		intron	N/A	NP_001278787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.2782+2408G>C		intron	N/A	ENSP00000497069.1
	IGF1R	ENST00000560972.1	TSL:1	n.85+2408G>C		intron	N/A
	IGF1R	ENST00000649865.1		c.2782+2408G>C		intron	N/A	ENSP00000496919.1

Frequencies

GnomAD3 genomes AF: 0.974 AC: 148213 AN: 152186 Hom.: 72207 Cov.: 32

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.986

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.978

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.974 AC: 148306 AN: 152304 Hom.: 72245 Cov.: 32 AF XY: 0.975 AC XY: 72590 AN XY: 74468

African (AFR) AF: 0.939 AC: 39001 AN: 41556

American (AMR) AF: 0.986 AC: 15087 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 3315 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5170 AN: 5172

South Asian (SAS) AF: 0.994 AC: 4795 AN: 4822

European-Finnish (FIN) AF: 0.987 AC: 10486 AN: 10620

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.987 AC: 67182 AN: 68036

Other (OTH) AF: 0.979 AC: 2069 AN: 2114

Alfa AF: 0.979 Hom.: 9047

Bravo AF: 0.971

Asia WGS AF: 0.991 AC: 3446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.52
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs1546714; hg19: chr15-99470321;