rs1549593

Variant names:

• chr12-102403013-G-T
• rs1549593
• NM_000618.5:c.403-447C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000618.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	NM_000618.5	MANE Select	c.403-447C>A		intron	N/A	NP_000609.1
	IGF1	NM_001111283.3		c.452-447C>A		intron	N/A	NP_001104753.1
	IGF1	NM_001414007.1		c.403-447C>A		intron	N/A	NP_001400936.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.403-447C>A		intron	N/A	ENSP00000337612.7
	IGF1	ENST00000424202.6	TSL:1	c.355-447C>A		intron	N/A	ENSP00000416811.2
	IGF1	ENST00000392904.5	TSL:5	c.452-447C>A		intron	N/A	ENSP00000376637.1

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

African (AFR) AF: 0.0252 AC: 1047 AN: 41510

American (AMR) AF: 0.203 AC: 3097 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0750 AC: 260 AN: 3468

East Asian (EAS) AF: 0.0152 AC: 79 AN: 5190

South Asian (SAS) AF: 0.164 AC: 790 AN: 4820

European-Finnish (FIN) AF: 0.178 AC: 1875 AN: 10524

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9579 AN: 67964

Other (OTH) AF: 0.0956 AC: 202 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.54
PhyloP100		0.12
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: rs1549593; hg19: chr12-102796791;