rs110402

Variant names:

• chr17-45802681-G-A
• rs110402
• NM_004382.5:c.34-4329G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-45802681-G-A
• chr17-45802681-G-C
• chr17-45802681-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004382.5(CRHR1):​c.34-4329G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,990 control chromosomes in the GnomAD database, including 16,858 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 0.45 (16858 hom., cov: 32)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 175 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.34-4329G>A		intron_variant	Intron 1 of 12	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.34-4329G>A		intron_variant	Intron 1 of 12	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.-492-4329G>A		intron_variant	Intron 3 of 14	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68615 AN: 151872 Hom.: 16854 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.452 AC: 68631 AN: 151990 Hom.: 16858 Cov.: 32 AF XY: 0.468 AC XY: 34781 AN XY: 74296

African (AFR) AF: 0.311 AC: 12882 AN: 41442

American (AMR) AF: 0.531 AC: 8121 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3468

East Asian (EAS) AF: 0.897 AC: 4624 AN: 5156

South Asian (SAS) AF: 0.700 AC: 3371 AN: 4818

European-Finnish (FIN) AF: 0.624 AC: 6591 AN: 10562

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30021 AN: 67944

Other (OTH) AF: 0.449 AC: 946 AN: 2106

Alfa AF: 0.444 Hom.: 63349

Bravo AF: 0.438

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	19
DANN	Benign	0.77
PhyloP100		1.2
Mutation Taster		=95/5	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: rs110402; hg19: chr17-43880047;