chr12-102481479-C-T

Position:

• chr12-102481479-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 71 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1	NM_001414005.1	c.-20+224G>A		intron_variant			NP_001400934.1
IGF1	NM_001414007.1	c.-20+224G>A		intron_variant			NP_001400936.1
IGF1	XM_017019259.2	c.114+224G>A		intron_variant			XP_016874748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000644491.1	c.-20+224G>A		intron_variant				ENSP00000494228.1

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

Gnomad4 AFR AF: 0.0346

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00457

Gnomad4 FIN AF: 0.0280

Gnomad4 NFE AF: 0.0223

Gnomad4 OTH AF: 0.0214

Alfa AF: 0.0156 Hom.: 6

Bravo AF: 0.0253

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11829693; hg19: chr12-102875257;