rs17688434

Variant names:

• chr17-45695174-G-A
• rs17688434
• ENST00000634540.1:c.-493+65016G>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+65016G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,144 control chromosomes in the GnomAD database, including 2,137 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 0.14 (2137 hom., cov: 32)
• Consequence: LINC02210-CRHR1 ENST00000634540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 26 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC02210-CRHR1	NM_001303016.1	c.-185+22272G>A		intron_variant	Intron 3 of 12		NP_001289945.1
LINC02210-CRHR1	NM_001256299.3	c.-493+65016G>A		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.-493+65016G>A		intron_variant	Intron 3 of 14	2		ENSP00000488912.1
LINC02210-CRHR1	ENST00000587305.1	n.447+22272G>A		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21825 AN: 152026 Hom.: 2139 Cov.: 32

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.143 AC: 21815 AN: 152144 Hom.: 2137 Cov.: 32 AF XY: 0.134 AC XY: 9991 AN XY: 74380

African (AFR) AF: 0.0429 AC: 1781 AN: 41520

American (AMR) AF: 0.176 AC: 2697 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 831 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5170

South Asian (SAS) AF: 0.0739 AC: 356 AN: 4820

European-Finnish (FIN) AF: 0.0649 AC: 687 AN: 10582

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14733 AN: 67984

Other (OTH) AF: 0.183 AC: 386 AN: 2114

Alfa AF: 0.197 Hom.: 1913

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.80
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17688434; hg19: chr17-43772540;