rs5742615

chr12-102477023-G-Achr12-102477023-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000618.5(IGF1):c.64-1224C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 152,170 control chromosomes in the GnomAD database, including 37 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 0.018 (37 hom., cov: 31)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0182 (2766/152170) while in subpopulation NFE AF= 0.0246 (1674/68002). AF 95% confidence interval is 0.0236. There are 37 homozygotes in gnomad4. There are 1276 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1	NM_000618.5	c.64-1224C>T		intron_variant		ENST00000337514.11
LINC02456	XR_007063427.1	n.28037G>A		non_coding_transcript_exon_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1	ENST00000337514.11	c.64-1224C>T		intron_variant		1	NM_000618.5	P1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2765 AN: 152052 Hom.: 36 Cov.: 31

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.00576

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0172

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

GnomAD4 genome AF: 0.0182 AC: 2766 AN: 152170 Hom.: 37 Cov.: 31 AF XY: 0.0171 AC XY: 1276 AN XY: 74412

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0123

Gnomad4 FIN AF: 0.00576

Gnomad4 NFE AF: 0.0246

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.00114 Hom.: 26

Bravo AF: 0.0192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	7.7
Dann	Benign	0.86

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: rs5742615; hg19: chr12-102870801;