12-102480984-A-T

Variant names:

• chr12-102480984-A-T
• rs2288377
• XR_007063427.1:n.31998A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007063427.1(LINC02456):​n.31998A>T 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 0.0345 in 152,178 control chromosomes in the GnomAD database, including 375 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 0.034 (375 hom., cov: 32)
• Consequence: LINC02456 XR_007063427.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 28 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC02456	XR_007063427.1	n.31998A>T		non_coding_transcript_exon_variant	Exon 11 of 13
IGF1	NM_001414005.1	c.-19-584T>A		intron_variant	Intron 1 of 4		NP_001400934.1
IGF1	NM_001414007.1	c.-19-584T>A		intron_variant	Intron 1 of 4		NP_001400936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1	ENST00000644491.1	c.-19-584T>A		intron_variant	Intron 1 of 4			ENSP00000494228.1

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5228 AN: 152060 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.00621

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0680

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.0903

Gnomad FIN AF: 0.0844

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0345 AC: 5248 AN: 152178 Hom.: 375 Cov.: 32 AF XY: 0.0396 AC XY: 2946 AN XY: 74386

African (AFR) AF: 0.00619 AC: 257 AN: 41528

American (AMR) AF: 0.0685 AC: 1047 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1569 AN: 5164

South Asian (SAS) AF: 0.0902 AC: 434 AN: 4814

European-Finnish (FIN) AF: 0.0844 AC: 895 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0138 AC: 937 AN: 68004

Other (OTH) AF: 0.0468 AC: 99 AN: 2114

Alfa AF: 0.0107 Hom.: 6

Bravo AF: 0.0342

Asia WGS AF: 0.218 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		0.093
PromoterAI		0.030	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2288377; hg19: chr12-102874762;