rs3743249

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-98962194-G-T
• chr15-98962194-G-A

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.*4752G>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 0.327 in 233,090 control chromosomes in the GnomAD database, including 13,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9971 hom., cov: 33)
  • Exomes 𝑓: 0.30 (3831 hom.)
• Consequence: IGF1R NM_000875.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.820
• 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=-0.83).
• BP6: Variant 15-98962194-G-T is Benign according to our data. Variant chr15-98962194-G-T is described in ClinVar as Benign. ClinVar VariationId is 317589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 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.*4752G>T		3_prime_UTR	Exon 21 of 21	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.*4752G>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.*4752G>T		3_prime_UTR	Exon 21 of 21	ENSP00000497069.1	P08069
	IGF1R	ENST00000649865.1		c.*4752G>T		3_prime_UTR	Exon 21 of 21	ENSP00000496919.1	C9J5X1
	SYNM-AS1	ENST00000559468.1	TSL:4	n.348+3795C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52126 AN: 151966 Hom.: 9949 Cov.: 33

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.297 AC: 24027 AN: 81006 Hom.: 3831 Cov.: 0 AF XY: 0.294 AC XY: 10949 AN XY: 37242

African (AFR) AF: 0.513 AC: 1996 AN: 3892

American (AMR) AF: 0.364 AC: 910 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1512 AN: 5126

East Asian (EAS) AF: 0.399 AC: 4555 AN: 11402

South Asian (SAS) AF: 0.286 AC: 201 AN: 702

European-Finnish (FIN) AF: 0.194 AC: 12 AN: 62

Middle Eastern (MID) AF: 0.297 AC: 146 AN: 492

European-Non Finnish (NFE) AF: 0.252 AC: 12629 AN: 50058

Other (OTH) AF: 0.305 AC: 2066 AN: 6772

GnomAD4 genome AF: 0.343 AC: 52184 AN: 152084 Hom.: 9971 Cov.: 33 AF XY: 0.344 AC XY: 25601 AN XY: 74362

African (AFR) AF: 0.511 AC: 21179 AN: 41480

American (AMR) AF: 0.366 AC: 5599 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3470

East Asian (EAS) AF: 0.466 AC: 2400 AN: 5154

South Asian (SAS) AF: 0.319 AC: 1542 AN: 4828

European-Finnish (FIN) AF: 0.212 AC: 2247 AN: 10588

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17055 AN: 67968

Other (OTH) AF: 0.321 AC: 677 AN: 2110

Alfa AF: 0.283 Hom.: 12114

Bravo AF: 0.361

Asia WGS AF: 0.378 AC: 1313 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.83
CADD	Benign	3.7
DANN	Benign	0.61
PhyloP100		0.82
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: rs3743249; hg19: chr15-99505423;