rs17879774

Variant names:

• chr12-102480643-T-A
• rs17879774
• XR_007063427.1:n.31657T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The XR_007063427.1(LINC02456):​n.31657T>A variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000596 in 1,173,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: LINC02456 XR_007063427.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.48
• Publications: 1 publications found

Genes affected

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

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]

IGF1 Gene-Disease associations (from GenCC):

• growth delay due to insulin-like growth factor type 1 deficiency

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000337514.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	NM_001414005.1		c.-19-243A>T		intron	N/A	NP_001400934.1
	IGF1	NM_001414007.1		c.-19-243A>T		intron	N/A	NP_001400936.1
	IGF1	NM_000618.5	MANE Select	c.-262A>T		upstream_gene	N/A	NP_000609.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000644491.1		c.-19-243A>T		intron	N/A	ENSP00000494228.1
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.-262A>T		upstream_gene	N/A	ENSP00000337612.7
	IGF1	ENST00000307046.8	TSL:1	c.-262A>T		upstream_gene	N/A	ENSP00000302665.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000596 AC: 7 AN: 1173694 Hom.: 0 Cov.: 22 AF XY: 0.00000354 AC XY: 2 AN XY: 565734

African (AFR) AF: 0.00 AC: 0 AN: 26270

American (AMR) AF: 0.00 AC: 0 AN: 16304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16438

East Asian (EAS) AF: 0.00 AC: 0 AN: 27932

South Asian (SAS) AF: 0.00 AC: 0 AN: 58480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3136

European-Non Finnish (NFE) AF: 0.00000729 AC: 7 AN: 960502

Other (OTH) AF: 0.00 AC: 0 AN: 47480

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.92
PhyloP100		7.5
PromoterAI		-0.20	Neutral

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: rs17879774; hg19: chr12-102874421;