rs8038415

Variant names:

• chr15-98956205-T-C
• rs8038415
• NM_000875.5:c.3723-856T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000875.5(IGF1R):​c.3723-856T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 152,172 control chromosomes in the GnomAD database, including 26,392 homozygotes. 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: 𝑓 0.58 (26392 hom., cov: 34)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5	c.3723-856T>C		intron_variant	Intron 20 of 20	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1	c.3723-856T>C		intron_variant	Intron 20 of 20		NM_000875.5	ENSP00000497069.1
IGF1R	ENST00000649865.1	c.3720-856T>C		intron_variant	Intron 20 of 20			ENSP00000496919.1
IGF1R	ENST00000558751.1	n.317-856T>C		intron_variant	Intron 1 of 1	4
SYNM-AS1	ENST00000559468.1	n.349-1817A>G		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87424 AN: 152054 Hom.: 26342 Cov.: 34

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.529

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.575 AC: 87527 AN: 152172 Hom.: 26392 Cov.: 34 AF XY: 0.571 AC XY: 42452 AN XY: 74400

African (AFR) AF: 0.772 AC: 32053 AN: 41530

American (AMR) AF: 0.563 AC: 8606 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3466

East Asian (EAS) AF: 0.490 AC: 2528 AN: 5158

South Asian (SAS) AF: 0.447 AC: 2158 AN: 4828

European-Finnish (FIN) AF: 0.457 AC: 4849 AN: 10600

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.499 AC: 33893 AN: 67988

Other (OTH) AF: 0.525 AC: 1110 AN: 2114

Alfa AF: 0.527 Hom.: 4375

Bravo AF: 0.594

Asia WGS AF: 0.510 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.27
PhyloP100		-2.1
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: rs8038415; hg19: chr15-99499434;