rs1549593

Positions:

• chr12-102403013-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000618.5(IGF1):​c.403-447C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,068 control chromosomes in the GnomAD database, including 1,268 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 0.11 (1268 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1	NM_000618.5	c.403-447C>A		intron_variant		ENST00000337514.11	NP_000609.1
LINC02456	XR_007063427.1	n.697-1100G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.403-447C>A		intron_variant		1	NM_000618.5	ENSP00000337612	P1
LINC02456	ENST00000704346.1	n.1067-20058G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16999 AN: 151950 Hom.: 1270 Cov.: 32

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.0750

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.0966

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

GnomAD4 genome AF: 0.112 AC: 16999 AN: 152068 Hom.: 1268 Cov.: 32 AF XY: 0.115 AC XY: 8555 AN XY: 74346

Gnomad4 AFR AF: 0.0252

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.0750

Gnomad4 EAS AF: 0.0152

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.0956

Alfa AF: 0.126 Hom.: 170

Bravo AF: 0.107

Asia WGS AF: 0.0840 AC: 293 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs1549593; hg19: chr12-102796791;