rs17847203

Variant names:

• chr15-98957376-C-T
• rs17847203
• NM_000875.5:c.4038C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-98957376-C-T
• chr15-98957376-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000875.5(IGF1R):​c.4038C>T​(p.Tyr1346Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 1,613,316 control chromosomes in the GnomAD database, including 2,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (487 hom., cov: 33)
  • Exomes 𝑓: 0.049 (2145 hom.)
• Consequence: IGF1R NM_000875.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.628
• Publications: 15 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 15-98957376-C-T is Benign according to our data. Variant chr15-98957376-C-T is described in ClinVar as Benign. ClinVar VariationId is 287436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.628 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 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.4038C>T	p.Tyr1346Tyr	synonymous	Exon 21 of 21	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.4035C>T	p.Tyr1345Tyr	synonymous	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.4038C>T	p.Tyr1346Tyr	synonymous	Exon 21 of 21	ENSP00000497069.1	P08069
	IGF1R	ENST00000649865.1		c.4035C>T	p.Tyr1345Tyr	synonymous	Exon 21 of 21	ENSP00000496919.1	C9J5X1
	SYNM-AS1	ENST00000559468.1	TSL:4	n.349-2988G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10372 AN: 152206 Hom.: 485 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.0856

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0345

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.0301

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.0473

GnomAD2 exomes AF: 0.0593 AC: 14784 AN: 249380 AF XY: 0.0561

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.0230

Gnomad EAS exome AF: 0.0341

Gnomad FIN exome AF: 0.0326

Gnomad NFE exome AF: 0.0432

Gnomad OTH exome AF: 0.0530

GnomAD4 exome AF: 0.0488 AC: 71363 AN: 1460992 Hom.: 2145 Cov.: 34 AF XY: 0.0491 AC XY: 35706 AN XY: 726808

African (AFR) AF: 0.123 AC: 4125 AN: 33480

American (AMR) AF: 0.110 AC: 4921 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 633 AN: 26132

East Asian (EAS) AF: 0.0298 AC: 1183 AN: 39698

South Asian (SAS) AF: 0.0711 AC: 6129 AN: 86252

European-Finnish (FIN) AF: 0.0353 AC: 1858 AN: 52640

Middle Eastern (MID) AF: 0.0368 AC: 212 AN: 5760

European-Non Finnish (NFE) AF: 0.0445 AC: 49490 AN: 1111934

Other (OTH) AF: 0.0466 AC: 2812 AN: 60382

GnomAD4 genome AF: 0.0682 AC: 10385 AN: 152324 Hom.: 487 Cov.: 33 AF XY: 0.0681 AC XY: 5072 AN XY: 74478

African (AFR) AF: 0.118 AC: 4893 AN: 41566

American (AMR) AF: 0.0858 AC: 1313 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3472

East Asian (EAS) AF: 0.0344 AC: 178 AN: 5174

South Asian (SAS) AF: 0.0636 AC: 307 AN: 4828

European-Finnish (FIN) AF: 0.0301 AC: 320 AN: 10624

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0441 AC: 2999 AN: 68028

Other (OTH) AF: 0.0468 AC: 99 AN: 2116

Alfa AF: 0.0550 Hom.: 181

Bravo AF: 0.0740

Asia WGS AF: 0.0610 AC: 211 AN: 3478

EpiCase AF: 0.0405

EpiControl AF: 0.0401

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Growth delay due to insulin-like growth factor I resistance (1)
-	-	1	IGF1R-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.6
DANN	Benign	0.87
PhyloP100		0.63
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: rs17847203; hg19: chr15-99500605; COSMIC: COSV51294127;