NM_000875.5:c.*1856C>T

Variant names:

• chr15-98959298-C-T
• rs1058696
• NM_000875.5:c.*1856C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000875.5(IGF1R):​c.*1856C>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 0.05 in 233,598 control chromosomes in the GnomAD database, including 374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (264 hom., cov: 33)
  • Exomes 𝑓: 0.045 (110 hom.)
• Consequence: IGF1R NM_000875.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24
• Publications: 8 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 15-98959298-C-T is Benign according to our data. Variant chr15-98959298-C-T is described in ClinVar as Benign. ClinVar VariationId is 317517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0775 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.*1856C>T		3_prime_UTR	Exon 21 of 21	NP_000866.1
	IGF1R	NM_001291858.2		c.*1856C>T		3_prime_UTR	Exon 21 of 21	NP_001278787.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.*1856C>T		3_prime_UTR	Exon 21 of 21	ENSP00000497069.1
	IGF1R	ENST00000649865.1		c.*1856C>T		3_prime_UTR	Exon 21 of 21	ENSP00000496919.1
	SYNM-AS1	ENST00000559468.1	TSL:4	n.349-4910G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 7975 AN: 152222 Hom.: 263 Cov.: 33

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.0644

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.0440

GnomAD4 exome AF: 0.0454 AC: 3693 AN: 81258 Hom.: 110 Cov.: 0 AF XY: 0.0445 AC XY: 1665 AN XY: 37422

African (AFR) AF: 0.0648 AC: 252 AN: 3886

American (AMR) AF: 0.0880 AC: 220 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 131 AN: 5112

East Asian (EAS) AF: 0.0580 AC: 661 AN: 11392

South Asian (SAS) AF: 0.0571 AC: 40 AN: 700

European-Finnish (FIN) AF: 0.0393 AC: 19 AN: 484

Middle Eastern (MID) AF: 0.0265 AC: 13 AN: 490

European-Non Finnish (NFE) AF: 0.0409 AC: 2044 AN: 49936

Other (OTH) AF: 0.0463 AC: 313 AN: 6758

GnomAD4 genome AF: 0.0524 AC: 7981 AN: 152340 Hom.: 264 Cov.: 33 AF XY: 0.0526 AC XY: 3918 AN XY: 74502

African (AFR) AF: 0.0568 AC: 2363 AN: 41570

American (AMR) AF: 0.0813 AC: 1244 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0230 AC: 80 AN: 3472

East Asian (EAS) AF: 0.0640 AC: 332 AN: 5188

South Asian (SAS) AF: 0.0696 AC: 336 AN: 4828

European-Finnish (FIN) AF: 0.0303 AC: 322 AN: 10626

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0443 AC: 3016 AN: 68034

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

Alfa AF: 0.0488 Hom.: 394

Bravo AF: 0.0558

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.46
CADD	Benign	12
DANN	Benign	0.77
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1058696; hg19: chr15-99502527;