12-102396788-C-CT

Variant names:

• chr12-102396788-C-CT
• rs200146786
• NM_000618.5:c.*5718dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000618.5(IGF1):​c.*5718dupA 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
• 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]

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

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IGF1	NM_000618.5	c.*5718dupA		3_prime_UTR_variant	Exon 4 of 4	ENST00000337514.11	NP_000609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.*5718dupA		3_prime_UTR_variant	Exon 4 of 4	1	NM_000618.5	ENSP00000337612.7
HELLPAR	ENST00000626826.1	n.199217dupT		non_coding_transcript_exon_variant	Exon 1 of 1	6
LINC02456	ENST00000635615.1	n.450-26270dupT		intron_variant	Intron 4 of 5	5
LINC02456	ENST00000704346.1	n.1067-26270dupT		intron_variant	Intron 9 of 10

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0137 AC: 92 AN: 6734

American (AMR) AF: 0.111 AC: 773 AN: 6988

Ashkenazi Jewish (ASJ) AF: 0.0185 AC: 160 AN: 8662

East Asian (EAS) AF: 0.221 AC: 4777 AN: 21622

South Asian (SAS) AF: 0.0544 AC: 152 AN: 2796

European-Finnish (FIN) AF: 0.0746 AC: 1433 AN: 19204

Middle Eastern (MID) AF: 0.0176 AC: 21 AN: 1196

European-Non Finnish (NFE) AF: 0.0236 AC: 3494 AN: 147950

Other (OTH) AF: 0.0459 AC: 705 AN: 15358

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00797 AC: 314 AN: 39386

American (AMR) AF: 0.108 AC: 1563 AN: 14438

Ashkenazi Jewish (ASJ) AF: 0.00775 AC: 26 AN: 3354

East Asian (EAS) AF: 0.291 AC: 1461 AN: 5020

South Asian (SAS) AF: 0.0641 AC: 292 AN: 4554

European-Finnish (FIN) AF: 0.0829 AC: 739 AN: 8918

Middle Eastern (MID) AF: 0.0110 AC: 3 AN: 272

European-Non Finnish (NFE) AF: 0.0193 AC: 1261 AN: 65412

Other (OTH) AF: 0.0493 AC: 97 AN: 1966

Alfa AF: 0.0101 Hom.: 6

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
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: rs200146786; hg19: chr12-102790566; COSMIC: COSV61703011;