12-102481791-A-G

Position:

• chr12-102481791-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007063427.1(LINC02456):​n.32805A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 150,184 control chromosomes in the GnomAD database, including 42,941 homozygotes. 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: 𝑓 0.75 (42935 hom., cov: 26)
  • Exomes 𝑓: 0.88 (6 hom.)
• Consequence: LINC02456 XR_007063427.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

Genes affected

LINC02456 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINC02456	XR_007063427.1	n.32805A>G		non_coding_transcript_exon_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000644491.1			upstream_gene_variant				ENSP00000494228	P1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 112212 AN: 150058 Hom.: 42935 Cov.: 26

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.772

GnomAD4 exome AF: 0.875 AC: 14 AN: 16 Hom.: 6 Cov.: 0 AF XY: 0.833 AC XY: 10 AN XY: 12

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.748 AC: 112256 AN: 150168 Hom.: 42935 Cov.: 26 AF XY: 0.747 AC XY: 54696 AN XY: 73174

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.787

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.842

Gnomad4 OTH AF: 0.768

Alfa AF: 0.820 Hom.: 94210

Bravo AF: 0.733

Asia WGS AF: 0.687 AC: 2378 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35767; hg19: chr12-102875569;