17-45777790-G-T

Variant names:

• chr17-45777790-G-T
• rs4074461
• ENST00000634540.1:c.-492-29220G>T

Variant summary

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

The NM_001303016.1(LINC02210-CRHR1):​c.-184-29220G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,912 control chromosomes in the GnomAD database, including 18,386 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 0.48 (18386 hom., cov: 31)
• Consequence: LINC02210-CRHR1 NM_001303016.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.27
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303016.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC02210-CRHR1	NM_001303016.1		c.-184-29220G>T		intron	N/A	NP_001289945.1
	LINC02210-CRHR1	NM_001256299.3		c.-492-29220G>T		intron	N/A	NP_001243228.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC02210-CRHR1	ENST00000634540.1	TSL:2	c.-492-29220G>T		intron	N/A	ENSP00000488912.1
	LINC02210-CRHR1	ENST00000587305.1	TSL:5	n.448-29220G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73211 AN: 151794 Hom.: 18360 Cov.: 31

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.482 AC: 73292 AN: 151912 Hom.: 18386 Cov.: 31 AF XY: 0.467 AC XY: 34636 AN XY: 74210

African (AFR) AF: 0.491 AC: 20321 AN: 41398

American (AMR) AF: 0.463 AC: 7068 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1882 AN: 3468

East Asian (EAS) AF: 0.120 AC: 617 AN: 5158

South Asian (SAS) AF: 0.264 AC: 1271 AN: 4816

European-Finnish (FIN) AF: 0.349 AC: 3679 AN: 10544

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36760 AN: 67936

Other (OTH) AF: 0.501 AC: 1056 AN: 2106

Alfa AF: 0.512 Hom.: 28734

Bravo AF: 0.492

Asia WGS AF: 0.232 AC: 809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.049
DANN	Benign	0.68
PhyloP100		-3.3
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: rs4074461; hg19: chr17-43855156;