NM_000875.5:c.*910C>T

Variant names:

• chr15-98958352-C-T
• rs702497
• NM_000875.5:c.*910C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000875.5(IGF1R):​c.*910C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 220,666 control chromosomes in the GnomAD database, including 4,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3007 hom., cov: 29)
  • Exomes 𝑓: 0.16 (1171 hom.)
• Consequence: IGF1R NM_000875.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.286
• Publications: 16 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-98958352-C-T is Benign according to our data. Variant chr15-98958352-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 317492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	NM_000875.5	MANE Select	c.*910C>T		3_prime_UTR	Exon 21 of 21	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.*910C>T		3_prime_UTR	Exon 21 of 21	NP_001278787.1	C9J5X1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.*910C>T		3_prime_UTR	Exon 21 of 21	ENSP00000497069.1	P08069
	IGF1R	ENST00000649865.1		c.*910C>T		3_prime_UTR	Exon 21 of 21	ENSP00000496919.1	C9J5X1
	SYNM-AS1	ENST00000559468.1	TSL:4	n.349-3964G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29129 AN: 151014 Hom.: 3005 Cov.: 29

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0240

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.160 AC: 11133 AN: 69544 Hom.: 1171 Cov.: 0 AF XY: 0.159 AC XY: 5094 AN XY: 32068

African (AFR) AF: 0.138 AC: 444 AN: 3226

American (AMR) AF: 0.160 AC: 332 AN: 2074

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 640 AN: 4442

East Asian (EAS) AF: 0.0233 AC: 245 AN: 10536

South Asian (SAS) AF: 0.0641 AC: 39 AN: 608

European-Finnish (FIN) AF: 0.250 AC: 15 AN: 60

Middle Eastern (MID) AF: 0.153 AC: 66 AN: 432

European-Non Finnish (NFE) AF: 0.198 AC: 8396 AN: 42366

Other (OTH) AF: 0.165 AC: 956 AN: 5800

GnomAD4 genome AF: 0.193 AC: 29148 AN: 151122 Hom.: 3007 Cov.: 29 AF XY: 0.189 AC XY: 13945 AN XY: 73766

African (AFR) AF: 0.157 AC: 6455 AN: 41124

American (AMR) AF: 0.183 AC: 2787 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3466

East Asian (EAS) AF: 0.0240 AC: 123 AN: 5118

South Asian (SAS) AF: 0.0709 AC: 338 AN: 4764

European-Finnish (FIN) AF: 0.249 AC: 2589 AN: 10390

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15585 AN: 67768

Other (OTH) AF: 0.189 AC: 397 AN: 2100

Alfa AF: 0.213 Hom.: 10510

Bravo AF: 0.190

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Growth delay due to insulin-like growth factor I resistance (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.59
PhyloP100		0.29
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: rs702497; hg19: chr15-99501581; COSMIC: COSV51274122; COSMIC: COSV51274122;