17-45771129-G-T

Variant names:

• chr17-45771129-G-T
• rs7225082
• ENST00000634540.1:c.-492-35881G>T

Variant summary

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

The ENST00000634540.1(LINC02210-CRHR1):​c.-492-35881G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,838 control chromosomes in the GnomAD database, including 27,512 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 0.59 (27512 hom., cov: 30)
• Consequence: LINC02210-CRHR1 ENST00000634540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 17 publications found

Genes affected

LINC02210-CRHR1 (HGNC:51483): (LINC02210-CRHR1 readthrough) This locus represents naturally occurring readthrough transcription between neighboring genes CRHR1-IT1, CRHR1 intronic transcript 1 (Gene ID: 147081) and CRHR1, corticotropin releasing hormone receptor 1 (Gene ID: 1394) on chromosome 17. The readthrough transcript encodes a protein that shares sequence identity with the product of the CRHR1 gene. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC02210-CRHR1	NM_001303016.1	c.-184-35881G>T		intron_variant	Intron 3 of 12		NP_001289945.1
LINC02210-CRHR1	NM_001256299.3	c.-492-35881G>T		intron_variant	Intron 3 of 14		NP_001243228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC02210-CRHR1	ENST00000634540.1	c.-492-35881G>T		intron_variant	Intron 3 of 14	2		ENSP00000488912.1
LINC02210-CRHR1	ENST00000587305.1	n.448-35881G>T		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88874 AN: 151720 Hom.: 27515 Cov.: 30

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.585 AC: 88886 AN: 151838 Hom.: 27512 Cov.: 30 AF XY: 0.592 AC XY: 43905 AN XY: 74148

African (AFR) AF: 0.376 AC: 15568 AN: 41408

American (AMR) AF: 0.671 AC: 10244 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2197 AN: 3466

East Asian (EAS) AF: 0.853 AC: 4388 AN: 5142

South Asian (SAS) AF: 0.758 AC: 3632 AN: 4792

European-Finnish (FIN) AF: 0.691 AC: 7283 AN: 10536

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.639 AC: 43437 AN: 67934

Other (OTH) AF: 0.606 AC: 1273 AN: 2102

Alfa AF: 0.599 Hom.: 40741

Bravo AF: 0.574

Asia WGS AF: 0.761 AC: 2645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.039
DANN	Benign	0.72
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs7225082; hg19: chr17-43848495;