ENST00000747123.1:n.177+3508C>A

Variant names:

• chr15-98643750-G-T
• rs1319868
• ENST00000747123.1:n.177+3508C>A

Variant summary

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

The ENST00000747123.1(IRAIN):​n.177+3508C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,134 control chromosomes in the GnomAD database, including 3,211 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 0.17 (3211 hom., cov: 32)
• Consequence: IRAIN ENST00000747123.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415
• Publications: 7 publications found

Genes affected

IRAIN (HGNC:50365): (IGF1R antisense imprinted non-protein coding RNA) This gene expresses a long non-coding RNA in antisense to the insulin-like growth factor type I receptor (IGF1R) gene. This transcript is imprinted and expressed from the paternal allele. It interacts with chromatin and may promote long-range DNA interactions that influence the regulation of gene expression. [provided by RefSeq, Nov 2015]

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 (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAIN	ENST00000747123.1	n.177+3508C>A		intron_variant	Intron 1 of 2
IRAIN	ENST00000747124.1	n.175+3508C>A		intron_variant	Intron 1 of 3
IRAIN	ENST00000747125.1	n.212+3508C>A		intron_variant	Intron 1 of 2
IRAIN	ENST00000747126.1	n.177+3508C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26064 AN: 152016 Hom.: 3199 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0898

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.172 AC: 26114 AN: 152134 Hom.: 3211 Cov.: 32 AF XY: 0.165 AC XY: 12237 AN XY: 74382

African (AFR) AF: 0.341 AC: 14140 AN: 41478

American (AMR) AF: 0.135 AC: 2067 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 644 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5180

South Asian (SAS) AF: 0.0899 AC: 433 AN: 4818

European-Finnish (FIN) AF: 0.0316 AC: 335 AN: 10614

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7941 AN: 67988

Other (OTH) AF: 0.153 AC: 322 AN: 2110

Alfa AF: 0.136 Hom.: 2822

Bravo AF: 0.188

Asia WGS AF: 0.0660 AC: 231 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	9.3
DANN	Benign	0.76
PhyloP100		-0.41

Splicing

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

Other links and lift over

dbSNP: rs1319868; hg19: chr15-99186979;