rs1396862

Variant names:

• chr17-45825631-G-A
• rs1396862
• NM_004382.5:c.328-3584G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-45825631-G-A
• chr17-45825631-G-C
• chr17-45825631-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.328-3584G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 154,556 control chromosomes in the GnomAD database, including 2,189 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 0.14 (2141 hom., cov: 33)
  • Exomes 𝑓: 0.19 (48 hom.)
• Consequence: CRHR1 NM_004382.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 60 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.328-3584G>A		intron_variant	Intron 4 of 12	ENST00000314537.10	NP_004373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.328-3584G>A		intron_variant	Intron 4 of 12	1	NM_004382.5	ENSP00000326060.6
LINC02210-CRHR1	ENST00000634540.1	c.-198-3584G>A		intron_variant	Intron 6 of 14	2		ENSP00000488912.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21851 AN: 152164 Hom.: 2143 Cov.: 33

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.190 AC: 433 AN: 2274 Hom.: 48 Cov.: 0 AF XY: 0.203 AC XY: 234 AN XY: 1150

African (AFR) AF: 0.0789 AC: 6 AN: 76

American (AMR) AF: 0.125 AC: 1 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.109 AC: 10 AN: 92

European-Finnish (FIN) AF: 0.0625 AC: 1 AN: 16

Middle Eastern (MID) AF: 0.205 AC: 335 AN: 1632

European-Non Finnish (NFE) AF: 0.225 AC: 55 AN: 244

Other (OTH) AF: 0.126 AC: 25 AN: 198

GnomAD4 genome AF: 0.143 AC: 21841 AN: 152282 Hom.: 2141 Cov.: 33 AF XY: 0.134 AC XY: 10003 AN XY: 74468

African (AFR) AF: 0.0430 AC: 1787 AN: 41578

American (AMR) AF: 0.176 AC: 2693 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.0744 AC: 359 AN: 4826

European-Finnish (FIN) AF: 0.0651 AC: 691 AN: 10618

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.217 AC: 14767 AN: 67986

Other (OTH) AF: 0.183 AC: 386 AN: 2114

Alfa AF: 0.192 Hom.: 5036

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.078
DANN	Benign	0.55
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1396862; hg19: chr17-43902997;