chr17-45729559-G-A

Variant names:

• chr17-45729559-G-A
• rs2902662
• ENST00000634540.1:c.-492-77451G>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.-492-77451G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,048 control chromosomes in the GnomAD database, including 2,202 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 (2202 hom., cov: 31)
• Consequence: LINC02210-CRHR1 ENST00000634540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• Publications: 23 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=-0.8).
• 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+56657G>A		intron_variant	Intron 3 of 12		NP_001289945.1
LINC02210-CRHR1	NM_001256299.3	c.-492-77451G>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.-492-77451G>A		intron_variant	Intron 3 of 14	2		ENSP00000488912.1
LINC02210-CRHR1	ENST00000587305.1	n.447+56657G>A		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22851 AN: 151930 Hom.: 2205 Cov.: 31

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.150 AC: 22846 AN: 152048 Hom.: 2202 Cov.: 31 AF XY: 0.141 AC XY: 10468 AN XY: 74344

African (AFR) AF: 0.0666 AC: 2764 AN: 41504

American (AMR) AF: 0.179 AC: 2737 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3464

East Asian (EAS) AF: 0.00156 AC: 8 AN: 5136

South Asian (SAS) AF: 0.0745 AC: 359 AN: 4816

European-Finnish (FIN) AF: 0.0652 AC: 691 AN: 10602

Middle Eastern (MID) AF: 0.221 AC: 64 AN: 290

European-Non Finnish (NFE) AF: 0.217 AC: 14738 AN: 67938

Other (OTH) AF: 0.189 AC: 398 AN: 2106

Alfa AF: 0.197 Hom.: 1917

Bravo AF: 0.156

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		0.25
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: rs2902662; hg19: chr17-43806925;