12-102396788-C-CT

Position:

• chr12-102396788-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000618.5(IGF1):​c.*5718_*5719insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 374,716 control chromosomes in the GnomAD database, including 363 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (362 hom., cov: 31)
  • Exomes 𝑓: 0.050 (1 hom.)
• Consequence: IGF1 NM_000618.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48

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]

HELLPAR (HGNC:43984): (HELLP associated long non-coding RNA)

LINC02456 (HGNC:53389): (long intergenic non-protein coding RNA 2456)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-102396788-C-CT is Benign according to our data. Variant chr12-102396788-C-CT is described in ClinVar as [Benign]. Clinvar id is 306838.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1	NM_000618.5	c.*5718_*5719insA		3_prime_UTR_variant	4/4	ENST00000337514.11
LINC02456	XR_007063427.1	n.697-7312dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1	ENST00000337514.11	c.*5718_*5719insA		3_prime_UTR_variant	4/4	1	NM_000618.5	P1
HELLPAR	ENST00000626826.1	n.199217dup		non_coding_transcript_exon_variant	1/1
LINC02456	ENST00000704346.1	n.1067-26270dup		intron_variant, non_coding_transcript_variant
LINC02456	ENST00000635615.1	n.450-26270dup		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 5734 AN: 144164 Hom.: 356 Cov.: 31

Gnomad AFR AF: 0.00799

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.00775

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.0638

Gnomad FIN AF: 0.0829

Gnomad MID AF: 0.0101

Gnomad NFE AF: 0.0193

Gnomad OTH AF: 0.0456

GnomAD4 exome AF: 0.0504 AC: 11607 AN: 230510 Hom.: 1 Cov.: 0 AF XY: 0.0488 AC XY: 5711 AN XY: 116916

Gnomad4 AFR exome AF: 0.0137

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.0185

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.0544

Gnomad4 FIN exome AF: 0.0746

Gnomad4 NFE exome AF: 0.0236

Gnomad4 OTH exome AF: 0.0459

GnomAD4 genome AF: 0.0399 AC: 5756 AN: 144206 Hom.: 362 Cov.: 31 AF XY: 0.0446 AC XY: 3124 AN XY: 70116

Gnomad4 AFR AF: 0.00797

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.00775

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.0641

Gnomad4 FIN AF: 0.0829

Gnomad4 NFE AF: 0.0193

Gnomad4 OTH AF: 0.0493

Bravo AF: 0.0406

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Growth delay due to insulin-like growth factor type 1 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs200146786; hg19: chr12-102790566;