rs436667

Variant names:

• chr17-45632049-C-T
• rs436667
• ENST00000634540.1:c.-493+1891C>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.-493+1891C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 148,270 control chromosomes in the GnomAD database, including 2,140 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 0.15 (2140 hom., cov: 31)
• Consequence: LINC02210-CRHR1 ENST00000634540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• 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]

LINC02210 (HGNC:):

LINC02210 (HGNC:26327): (long intergenic non-protein coding RNA 2210)

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 (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC02210-CRHR1	NM_001303016.1	c.-261+1891C>T		intron_variant	Intron 2 of 12		NP_001289945.1
LINC02210-CRHR1	NM_001256299.3	c.-493+1891C>T		intron_variant	Intron 3 of 14		NP_001243228.1
LINC02210	NR_026680.3	n.433+1891C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC02210-CRHR1	ENST00000634540.1	c.-493+1891C>T		intron_variant	Intron 3 of 14	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 21808 AN: 148188 Hom.: 2142 Cov.: 31

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.0796

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.147 AC: 21798 AN: 148270 Hom.: 2140 Cov.: 31 AF XY: 0.138 AC XY: 9976 AN XY: 72256

African (AFR) AF: 0.0440 AC: 1780 AN: 40478

American (AMR) AF: 0.180 AC: 2685 AN: 14918

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 832 AN: 3448

East Asian (EAS) AF: 0.00194 AC: 9 AN: 4640

South Asian (SAS) AF: 0.0795 AC: 354 AN: 4452

European-Finnish (FIN) AF: 0.0695 AC: 683 AN: 9834

Middle Eastern (MID) AF: 0.224 AC: 64 AN: 286

European-Non Finnish (NFE) AF: 0.219 AC: 14724 AN: 67222

Other (OTH) AF: 0.183 AC: 381 AN: 2086

Alfa AF: 0.198 Hom.: 1312

Bravo AF: 0.149

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	-0.89
CADD	Benign	2.0
DANN	Benign	0.77
PhyloP100		-0.30
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: rs436667; hg19: chr17-43709415;