ENST00000634540.1:c.-492-29874A>G

Variant names:

• chr17-45777136-A-G
• rs12938031
• ENST00000634540.1:c.-492-29874A>G

Variant summary

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

The ENST00000634540.1(LINC02210-CRHR1):​c.-492-29874A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,236 control chromosomes in the GnomAD database, including 6,512 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 0.26 (6512 hom., cov: 33)
• Consequence: LINC02210-CRHR1 ENST00000634540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723
• Publications: 32 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC02210-CRHR1	NM_001303016.1	c.-184-29874A>G		intron_variant	Intron 3 of 12		NP_001289945.1
LINC02210-CRHR1	NM_001256299.3	c.-492-29874A>G		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.-492-29874A>G		intron_variant	Intron 3 of 14	2		ENSP00000488912.1
LINC02210-CRHR1	ENST00000587305.1	n.448-29874A>G		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39570 AN: 152118 Hom.: 6513 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.260 AC: 39577 AN: 152236 Hom.: 6512 Cov.: 33 AF XY: 0.245 AC XY: 18248 AN XY: 74424

African (AFR) AF: 0.107 AC: 4446 AN: 41558

American (AMR) AF: 0.268 AC: 4096 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3470

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5188

South Asian (SAS) AF: 0.183 AC: 881 AN: 4824

European-Finnish (FIN) AF: 0.170 AC: 1806 AN: 10606

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25983 AN: 67986

Other (OTH) AF: 0.282 AC: 596 AN: 2114

Alfa AF: 0.352 Hom.: 15740

Bravo AF: 0.260

Asia WGS AF: 0.102 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.44
PhyloP100		-0.72
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: rs12938031; hg19: chr17-43854502;