rs171440

Variant names:

• chr17-45816121-G-A
• rs171440
• NM_004382.5:c.122-342G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-45816121-G-A
• chr17-45816121-G-C
• chr17-45816121-G-T

Variant summary

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

The NM_004382.5(CRHR1):​c.122-342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,952 control chromosomes in the GnomAD database, including 19,036 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 0.49 (19036 hom., cov: 31)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 29 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.122-342G>A		intron_variant	Intron 2 of 12	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.122-342G>A		intron_variant	Intron 2 of 12	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.-404-342G>A		intron_variant	Intron 4 of 14	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73950 AN: 151834 Hom.: 19032 Cov.: 31

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.487 AC: 73969 AN: 151952 Hom.: 19036 Cov.: 31 AF XY: 0.503 AC XY: 37337 AN XY: 74260

African (AFR) AF: 0.377 AC: 15612 AN: 41440

American (AMR) AF: 0.558 AC: 8521 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1645 AN: 3466

East Asian (EAS) AF: 0.864 AC: 4455 AN: 5156

South Asian (SAS) AF: 0.703 AC: 3377 AN: 4802

European-Finnish (FIN) AF: 0.666 AC: 7031 AN: 10556

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31778 AN: 67946

Other (OTH) AF: 0.479 AC: 1011 AN: 2112

Alfa AF: 0.471 Hom.: 45123

Bravo AF: 0.474

Asia WGS AF: 0.750 AC: 2605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		0.36
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: rs171440; hg19: chr17-43893487;