rs17884646

Variant names:

• chr12-102452037-C-T
• rs17884646
• NM_000618.5:c.220+23606G>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.220+23606G>A variant causes a intron change. The variant allele was found at a frequency of 0.0523 in 151,978 control chromosomes in the GnomAD database, including 322 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 0.052 (322 hom., cov: 29)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0792 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	NM_000618.5	MANE Select	c.220+23606G>A		intron	N/A	NP_000609.1	Q5U743
	IGF1	NM_001111285.3		c.220+23606G>A		intron	N/A	NP_001104755.1	P05019-1
	IGF1	NM_001414005.1		c.220+23606G>A		intron	N/A	NP_001400934.1	P05019-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.220+23606G>A		intron	N/A	ENSP00000337612.7	P05019-2
	IGF1	ENST00000307046.8	TSL:1	c.220+23606G>A		intron	N/A	ENSP00000302665.8	P05019-1
	IGF1	ENST00000424202.6	TSL:1	c.172+23606G>A		intron	N/A	ENSP00000416811.2	P05019-3

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 7953 AN: 151860 Hom.: 322 Cov.: 29

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00997

Gnomad FIN AF: 0.0306

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.0725

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

GnomAD4 genome AF: 0.0523 AC: 7953 AN: 151978 Hom.: 322 Cov.: 29 AF XY: 0.0501 AC XY: 3723 AN XY: 74272

African (AFR) AF: 0.0165 AC: 685 AN: 41494

American (AMR) AF: 0.0581 AC: 888 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 175 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00998 AC: 48 AN: 4812

European-Finnish (FIN) AF: 0.0306 AC: 322 AN: 10540

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0810 AC: 5502 AN: 67906

Other (OTH) AF: 0.0717 AC: 151 AN: 2106

Alfa AF: 0.0602 Hom.: 35

Bravo AF: 0.0544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.7
DANN	Benign	0.96
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: rs17884646; hg19: chr12-102845815;