12-102396788-CTTT-CTT

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

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

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

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	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: 0.00 AC: 562 AN: 143724 Hom.: 0 Cov.: 31 FAILED QC

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

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.408

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.358

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.377

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

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.00319

Gnomad4 ASJ AF: 0.00330

Gnomad4 EAS AF: 0.000797

Gnomad4 SAS AF: 0.00110

Gnomad4 FIN AF: 0.0200

Gnomad4 NFE AF: 0.00410

Gnomad4 OTH AF: 0.00204

ClinVar

Not reported in ClinVar

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;