rs5742615

Variant names:

• chr12-102477023-G-A
• rs5742615
• NM_000618.5:c.64-1224C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-102477023-G-A
• chr12-102477023-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000618.5(IGF1):​c.64-1224C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 152,170 control chromosomes in the GnomAD database, including 37 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 0.018 (37 hom., cov: 31)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 6 publications found

Genes affected

IGF1 (HGNC:5464): (insulin like growth factor 1) The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]

LINC02456 (HGNC:53389): (long intergenic non-protein coding RNA 2456)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0182 (2766/152170) while in subpopulation NFE AF = 0.0246 (1674/68002). AF 95% confidence interval is 0.0236. There are 37 homozygotes in GnomAd4. There are 1276 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 37 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.64-1224C>T		intron_variant	Intron 1 of 3	ENST00000337514.11	NP_000609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.64-1224C>T		intron_variant	Intron 1 of 3	1	NM_000618.5	ENSP00000337612.7

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2765 AN: 152052 Hom.: 36 Cov.: 31

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.00576

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0172

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

GnomAD4 genome AF: 0.0182 AC: 2766 AN: 152170 Hom.: 37 Cov.: 31 AF XY: 0.0171 AC XY: 1276 AN XY: 74412

African (AFR) AF: 0.0168 AC: 698 AN: 41530

American (AMR) AF: 0.0112 AC: 171 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.0123 AC: 59 AN: 4814

European-Finnish (FIN) AF: 0.00576 AC: 61 AN: 10594

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0246 AC: 1674 AN: 68002

Other (OTH) AF: 0.0171 AC: 36 AN: 2110

Alfa AF: 0.00114 Hom.: 26

Bravo AF: 0.0192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.7
DANN	Benign	0.86
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism

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: rs5742615; hg19: chr12-102870801;