rs4723000

Variant names:

• chr7-30662298-G-A
• rs4723000
• NM_001883.5:c.698-82C>T

Variant summary

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

The NM_001883.5(CRHR2):​c.698-82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,500,032 control chromosomes in the GnomAD database, including 14,242 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 0.15 (1939 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12303 hom.)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477
• Publications: 8 publications found

Genes affected

CRHR2 (HGNC:2358): (corticotropin releasing hormone receptor 2) The protein encoded by this gene belongs to the G-protein coupled receptor 2 family, and the subfamily of corticotropin releasing hormone receptor. This receptor shows high affinity for corticotropin releasing hormone (CRH), and also binds CRH-related peptides such as urocortin. CRH is synthesized in the hypothalamus, and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge. Studies in mice suggest that this receptor maybe involved in mediating cardiovascular homeostasis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jan 2011]

ENSG00000305335 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.698-82C>T		intron_variant	Intron 6 of 11	ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.698-82C>T		intron_variant	Intron 6 of 11	1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22906 AN: 152026 Hom.: 1928 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0696

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.130 AC: 175826 AN: 1347888 Hom.: 12303 AF XY: 0.132 AC XY: 89474 AN XY: 676204

African (AFR) AF: 0.230 AC: 7119 AN: 30950

American (AMR) AF: 0.0980 AC: 4287 AN: 43752

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3011 AN: 25088

East Asian (EAS) AF: 0.189 AC: 7377 AN: 39068

South Asian (SAS) AF: 0.188 AC: 15658 AN: 83132

European-Finnish (FIN) AF: 0.0728 AC: 3849 AN: 52858

Middle Eastern (MID) AF: 0.148 AC: 815 AN: 5512

European-Non Finnish (NFE) AF: 0.124 AC: 125755 AN: 1010958

Other (OTH) AF: 0.141 AC: 7955 AN: 56570

GnomAD4 genome AF: 0.151 AC: 22948 AN: 152144 Hom.: 1939 Cov.: 33 AF XY: 0.149 AC XY: 11063 AN XY: 74380

African (AFR) AF: 0.223 AC: 9266 AN: 41484

American (AMR) AF: 0.125 AC: 1909 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3472

East Asian (EAS) AF: 0.172 AC: 885 AN: 5150

South Asian (SAS) AF: 0.192 AC: 928 AN: 4824

European-Finnish (FIN) AF: 0.0696 AC: 737 AN: 10594

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8259 AN: 68010

Other (OTH) AF: 0.172 AC: 362 AN: 2110

Alfa AF: 0.145 Hom.: 648

Bravo AF: 0.158

Asia WGS AF: 0.220 AC: 765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.18
PhyloP100		-0.48
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: rs4723000; hg19: chr7-30701914;