17-45699947-A-G

Variant names:

• chr17-45699947-A-G
• rs1724422
• ENST00000634540.1:c.-493+69789A>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.-493+69789A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,034 control chromosomes in the GnomAD database, including 16,987 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 0.46 (16987 hom., cov: 32)
• Consequence: LINC02210-CRHR1 ENST00000634540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548
• Publications: 30 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000634540.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC02210-CRHR1	NM_001303016.1		c.-185+27045A>G		intron	N/A	NP_001289945.1
	LINC02210-CRHR1	NM_001256299.3		c.-493+69789A>G		intron	N/A	NP_001243228.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC02210-CRHR1	ENST00000634540.1	TSL:2	c.-493+69789A>G		intron	N/A	ENSP00000488912.1
	LINC02210-CRHR1	ENST00000587305.1	TSL:5	n.447+27045A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70265 AN: 151916 Hom.: 16979 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.463 AC: 70320 AN: 152034 Hom.: 16987 Cov.: 32 AF XY: 0.449 AC XY: 33384 AN XY: 74310

African (AFR) AF: 0.581 AC: 24106 AN: 41470

American (AMR) AF: 0.443 AC: 6768 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1649 AN: 3470

East Asian (EAS) AF: 0.179 AC: 924 AN: 5174

South Asian (SAS) AF: 0.247 AC: 1193 AN: 4824

European-Finnish (FIN) AF: 0.310 AC: 3280 AN: 10574

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30798 AN: 67916

Other (OTH) AF: 0.492 AC: 1041 AN: 2114

Alfa AF: 0.455 Hom.: 64411

Bravo AF: 0.481

Asia WGS AF: 0.249 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.72
DANN	Benign	0.58
PhyloP100		-0.55
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: rs1724422; hg19: chr17-43777313;