12-102396788-CTTT-CTT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000618.5(IGF1):​c.*5718delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0040 (0 hom., cov: 31)
  • Exomes 𝑓: 0.37 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IGF1 NM_000618.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 562 AN: 143724 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00320

Gnomad ASJ AF: 0.00330

Gnomad EAS AF: 0.000596

Gnomad SAS AF: 0.00109

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.00676

Gnomad NFE AF: 0.00408

Gnomad OTH AF: 0.00205

GnomAD4 exome AF: 0.373 AC: 72818 AN: 195038 Hom.: 0 Cov.: 0 AF XY: 0.376 AC XY: 37189 AN XY: 99018

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

African (AFR) AF: 0.407 AC: 2237 AN: 5492

American (AMR) AF: 0.317 AC: 1965 AN: 6206

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 2932 AN: 7180

East Asian (EAS) AF: 0.225 AC: 4352 AN: 19368

South Asian (SAS) AF: 0.358 AC: 860 AN: 2404

European-Finnish (FIN) AF: 0.342 AC: 5624 AN: 16430

Middle Eastern (MID) AF: 0.402 AC: 412 AN: 1024

European-Non Finnish (NFE) AF: 0.400 AC: 49484 AN: 123810

Other (OTH) AF: 0.377 AC: 4952 AN: 13124

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00396 AC: 570 AN: 143764 Hom.: 0 Cov.: 31 AF XY: 0.00438 AC XY: 306 AN XY: 69840

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

African (AFR) AF: 0.00137 AC: 54 AN: 39344

American (AMR) AF: 0.00319 AC: 46 AN: 14402

Ashkenazi Jewish (ASJ) AF: 0.00330 AC: 11 AN: 3338

East Asian (EAS) AF: 0.000797 AC: 4 AN: 5020

South Asian (SAS) AF: 0.00110 AC: 5 AN: 4554

European-Finnish (FIN) AF: 0.0200 AC: 176 AN: 8820

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

European-Non Finnish (NFE) AF: 0.00410 AC: 267 AN: 65164

Other (OTH) AF: 0.00204 AC: 4 AN: 1964

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism

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: COSV61706636;