12-102481479-C-T

Variant names:

• chr12-102481479-C-T
• rs11829693
• NM_001414005.1:c.-20+224G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001414005.1(IGF1):​c.-20+224G>A variant causes a intron change. The variant allele was found at a frequency of 0.0247 in 151,962 control chromosomes in the GnomAD database, including 71 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 0.025 (71 hom., cov: 31)
• Consequence: IGF1 NM_001414005.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.64
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0247 (3753/151962) while in subpopulation AFR AF = 0.0346 (1432/41436). AF 95% confidence interval is 0.0331. There are 71 homozygotes in GnomAd4. There are 1816 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 71 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414005.1. 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_001414005.1		c.-20+224G>A		intron	N/A	NP_001400934.1	P05019-1
	IGF1	NM_001414007.1		c.-20+224G>A		intron	N/A	NP_001400936.1	Q5U743

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000644491.1		c.-20+224G>A		intron	N/A	ENSP00000494228.1	P05019-2

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3751 AN: 151844 Hom.: 71 Cov.: 31

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0223

Gnomad OTH AF: 0.0216

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

GnomAD4 genome AF: 0.0247 AC: 3753 AN: 151962 Hom.: 71 Cov.: 31 AF XY: 0.0244 AC XY: 1816 AN XY: 74288

African (AFR) AF: 0.0346 AC: 1432 AN: 41436

American (AMR) AF: 0.0190 AC: 290 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00457 AC: 22 AN: 4812

European-Finnish (FIN) AF: 0.0280 AC: 295 AN: 10554

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0223 AC: 1517 AN: 67964

Other (OTH) AF: 0.0214 AC: 45 AN: 2106

Alfa AF: 0.0207 Hom.: 23

Bravo AF: 0.0253

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.84
PhyloP100		4.6
PromoterAI		-0.015	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11829693; hg19: chr12-102875257;