chr15-98962194-G-A

Variant names:

• chr15-98962194-G-A
• rs3743249
• NM_000875.5:c.*4752G>A

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.*4752G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 81,022 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: 0.000012 (0 hom.)
• Consequence: IGF1R NM_000875.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.820
• 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]

SYNM-AS1 (HGNC:55421): (SYNM antisense RNA 1)

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=-0.82).

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.*4752G>A		3_prime_UTR	Exon 21 of 21	NP_000866.1
	IGF1R	NM_001291858.2		c.*4752G>A		3_prime_UTR	Exon 21 of 21	NP_001278787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.*4752G>A		3_prime_UTR	Exon 21 of 21	ENSP00000497069.1
	IGF1R	ENST00000649865.1		c.*4752G>A		3_prime_UTR	Exon 21 of 21	ENSP00000496919.1
	SYNM-AS1	ENST00000559468.1	TSL:4	n.348+3795C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000123 AC: 1 AN: 81022 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 37250

African (AFR) AF: 0.00 AC: 0 AN: 3896

American (AMR) AF: 0.00 AC: 0 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5126

East Asian (EAS) AF: 0.0000877 AC: 1 AN: 11408

South Asian (SAS) AF: 0.00 AC: 0 AN: 702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 62

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 492

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 50064

Other (OTH) AF: 0.00 AC: 0 AN: 6772

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		0.82

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: rs3743249; hg19: chr15-99505423;