rs28364032

Variant names:

• chr17-45834976-G-A
• rs28364032
• ENST00000580955.6:n.1675G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-45834976-G-A
• chr17-45834976-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000580955.6(CRHR1):​n.1675G>A variant causes a non coding transcript exon 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 ENST00000580955.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.804
• Publications: 7 publications found

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]

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.*212G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.*212G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	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.: 33

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.: 6 AF XY: 0.0794 AC XY: 19352 AN XY: 243732

African (AFR) AF: 0.0765 AC: 991 AN: 12948

American (AMR) AF: 0.0792 AC: 1402 AN: 17702

Ashkenazi Jewish (ASJ) AF: 0.0542 AC: 726 AN: 13406

East Asian (EAS) AF: 0.124 AC: 3753 AN: 30360

South Asian (SAS) AF: 0.0877 AC: 3382 AN: 38566

European-Finnish (FIN) AF: 0.109 AC: 3151 AN: 28964

Middle Eastern (MID) AF: 0.0728 AC: 148 AN: 2034

European-Non Finnish (NFE) AF: 0.0707 AC: 21347 AN: 302010

Other (OTH) AF: 0.0768 AC: 2035 AN: 26506

GnomAD4 genome AF: 0.0767 AC: 11675 AN: 152228 Hom.: 485 Cov.: 33 AF XY: 0.0801 AC XY: 5958 AN XY: 74426

African (AFR) AF: 0.0743 AC: 3087 AN: 41538

American (AMR) AF: 0.0775 AC: 1186 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0496 AC: 172 AN: 3468

East Asian (EAS) AF: 0.121 AC: 627 AN: 5172

South Asian (SAS) AF: 0.0926 AC: 447 AN: 4828

European-Finnish (FIN) AF: 0.110 AC: 1167 AN: 10620

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4774 AN: 67980

Other (OTH) AF: 0.0719 AC: 152 AN: 2114

Alfa AF: 0.0697 Hom.: 653

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.3
DANN	Benign	0.44
PhyloP100		0.80
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: rs28364032; hg19: chr17-43912342; COSMIC: COSV53276525; COSMIC: COSV53276525;