ENST00000634540.1:c.-492-79182T>G

Variant names:

• chr17-45727828-T-G
• rs9303521
• ENST00000634540.1:c.-492-79182T>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.-492-79182T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 146,376 control chromosomes in the GnomAD database, including 26,410 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 0.59 (26410 hom., cov: 27)
• Consequence: LINC02210-CRHR1 ENST00000634540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 61 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC02210-CRHR1	NM_001303016.1	c.-185+54926T>G		intron_variant	Intron 3 of 12		NP_001289945.1
LINC02210-CRHR1	NM_001256299.3	c.-492-79182T>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.-492-79182T>G		intron_variant	Intron 3 of 14	2		ENSP00000488912.1
LINC02210-CRHR1	ENST00000587305.1	n.447+54926T>G		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.594 AC: 86874 AN: 146282 Hom.: 26391 Cov.: 27

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.594 AC: 86926 AN: 146376 Hom.: 26410 Cov.: 27 AF XY: 0.595 AC XY: 42363 AN XY: 71232

African (AFR) AF: 0.769 AC: 29760 AN: 38698

American (AMR) AF: 0.490 AC: 7320 AN: 14930

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1742 AN: 3424

East Asian (EAS) AF: 0.579 AC: 2908 AN: 5026

South Asian (SAS) AF: 0.632 AC: 2909 AN: 4606

European-Finnish (FIN) AF: 0.580 AC: 5640 AN: 9724

Middle Eastern (MID) AF: 0.448 AC: 130 AN: 290

European-Non Finnish (NFE) AF: 0.524 AC: 34992 AN: 66752

Other (OTH) AF: 0.554 AC: 1123 AN: 2028

Alfa AF: 0.554 Hom.: 98175

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		0.58
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: rs9303521; hg19: chr17-43805194;