ENST00000634540.1:c.-493+44389G>A

Variant names:

• chr17-45674547-G-A
• rs1635291
• ENST00000634540.1:c.-493+44389G>A

Variant summary

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

The ENST00000634540.1(LINC02210-CRHR1):​c.-493+44389G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 151,084 control chromosomes in the GnomAD database, including 39,135 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 0.70 (39135 hom., cov: 27)
• Consequence: LINC02210-CRHR1 ENST00000634540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375
• Publications: 44 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000634540.1. 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
	LINC02210-CRHR1	NM_001303016.1		c.-185+1645G>A		intron	N/A	NP_001289945.1
	LINC02210-CRHR1	NM_001256299.3		c.-493+44389G>A		intron	N/A	NP_001243228.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC02210-CRHR1	ENST00000634540.1	TSL:2	c.-493+44389G>A		intron	N/A	ENSP00000488912.1
	LINC02210-CRHR1	ENST00000587305.1	TSL:5	n.447+1645G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.701 AC: 105886 AN: 150966 Hom.: 39116 Cov.: 27

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.701 AC: 105940 AN: 151084 Hom.: 39135 Cov.: 27 AF XY: 0.717 AC XY: 52893 AN XY: 73792

African (AFR) AF: 0.460 AC: 18892 AN: 41036

American (AMR) AF: 0.764 AC: 11571 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2539 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5113 AN: 5148

South Asian (SAS) AF: 0.901 AC: 4316 AN: 4790

European-Finnish (FIN) AF: 0.926 AC: 9611 AN: 10380

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51644 AN: 67814

Other (OTH) AF: 0.698 AC: 1460 AN: 2092

Alfa AF: 0.738 Hom.: 130148

Bravo AF: 0.676

Asia WGS AF: 0.907 AC: 3153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.57
PhyloP100		0.38
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: rs1635291; hg19: chr17-43751913;