dbSNP rs28364032: CRHR1:c.*212G>A (chr17-45834976-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004382.5(CRHR1):c.*212G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 624,724 control chromosomes in the GnomAD database, including 2,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 485 hom., cov: 33)

Exomes 𝑓: 0.078 ( 1542 hom. )

Consequence

CRHR1
NM_004382.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.804

Variant links:

Genes affected

CRHR1 (HGNC:2357): (corticotropin releasing hormone receptor 1) This gene encodes a G-protein coupled receptor that binds neuropeptides of the corticotropin releasing hormone family that are major regulators of the hypothalamic-pituitary-adrenal pathway. The encoded protein is essential for the activation of signal transduction pathways that regulate diverse physiological processes including stress, reproduction, immune response and obesity. Alternative splicing results in multiple transcript variants. Naturally-occurring readthrough transcription between this gene and upstream GeneID:147081 results in transcripts that encode isoforms that share similarity with the products of this gene. [provided by RefSeq, Aug 2016]

CRHR1 links:

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]

LINC02210-CRHR1 links:

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

MAPT-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-45834976-G-A is Benign according to our data. Variant chr17-45834976-G-A is described in ClinVar as [Benign]. Clinvar id is 1220555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5 link	c.*212G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000314537.10	NP_004373.2	P34998-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10 link	c.*212G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_004382.5	ENSP00000326060.6		P34998-2
LINC02210-CRHR1	ENST00000634540.1 link	c.*212G>A		3_prime_UTR_variant	Exon 15 of 15	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes

AF:

0.0767

AC:

11661

AN:

152110

Hom.:

483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0742

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0777

Gnomad ASJ

AF:

0.0496

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0931

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0702

Gnomad OTH

AF:

0.0698

GnomAD4 exome

AF:

0.0782

AC:

36935

AN:

472496

Hom.:

1542

Cov.:

AF XY:

0.0794

AC XY:

19352

AN XY:

243732

show subpopulations

Gnomad4 AFR exome

AF:

0.0765

Gnomad4 AMR exome

AF:

0.0792

Gnomad4 ASJ exome

AF:

0.0542

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.0877

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.0707

Gnomad4 OTH exome

AF:

0.0768

GnomAD4 genome

AF:

0.0767

AC:

11675

AN:

152228

Hom.:

485

Cov.:

AF XY:

0.0801

AC XY:

5958

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0743

Gnomad4 AMR

AF:

0.0775

Gnomad4 ASJ

AF:

0.0496

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.0926

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.0702

Gnomad4 OTH

AF:

0.0719

Alfa

AF:

0.0493

Hom.:

Bravo

AF:

0.0744

Asia WGS

AF:

0.110

AC:

382

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 15, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24422887) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.3

DANN

Benign

0.44

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over