chr12-102396014-AGTC-TATTCAATTAGTTACATTTTAG

Position:

• chr12-102396014-AGTC-TATTCAATTAGTTACATTTTAG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000618.5(IGF1):​c.*6490_*6493delinsCTAAAATGTAACTAATTGAATA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGF1 NM_000618.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1	NM_000618.5	c.*6490_*6493delinsCTAAAATGTAACTAATTGAATA		3_prime_UTR_variant	4/4	ENST00000337514.11	NP_000609.1
LINC02456	XR_007063427.1	n.697-8099_697-8096delinsTATTCAATTAGTTACATTTTAG		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000337514.11	c.*6490_*6493delinsCTAAAATGTAACTAATTGAATA		3_prime_UTR_variant	4/4	1	NM_000618.5	ENSP00000337612	P1
HELLPAR	ENST00000626826.1	n.198430_198433delinsTATTCAATTAGTTACATTTTAG		non_coding_transcript_exon_variant	1/1
LINC02456	ENST00000704346.1	n.1067-27057_1067-27054delinsTATTCAATTAGTTACATTTTAG		intron_variant, non_coding_transcript_variant
LINC02456	ENST00000635615.1	n.450-27057_450-27054delinsTATTCAATTAGTTACATTTTAG		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs886048856; hg19: chr12-102789792;