rs4723003

Variant names:

• chr7-30686125-C-T
• rs4723003
• ENST00000348438.8:c.184+3066G>A

Variant summary

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

The ENST00000348438.8(CRHR2):​c.184+3066G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,242 control chromosomes in the GnomAD database, including 1,186 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 0.12 (1186 hom., cov: 33)
• Consequence: CRHR2 ENST00000348438.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901608	XR_007060275.1	n.864C>T		non_coding_transcript_exon_variant	Exon 2 of 2
CRHR2	NM_001202475.1	c.184+3066G>A		intron_variant	Intron 2 of 12		NP_001189404.1
CRHR2	NM_001202481.1	c.61+264G>A		intron_variant	Intron 3 of 13		NP_001189410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000348438.8	c.184+3066G>A		intron_variant	Intron 2 of 12	1		ENSP00000340943.4
CRHR2	ENST00000445981.5	c.184+3066G>A		intron_variant	Intron 2 of 2	1		ENSP00000401241.1
CRHR2	ENST00000423776.1	n.*216+264G>A		intron_variant	Intron 3 of 3	1		ENSP00000416620.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17800 AN: 152122 Hom.: 1179 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.117 AC: 17823 AN: 152242 Hom.: 1186 Cov.: 33 AF XY: 0.117 AC XY: 8712 AN XY: 74428

African (AFR) AF: 0.169 AC: 7007 AN: 41550

American (AMR) AF: 0.0786 AC: 1202 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 340 AN: 3472

East Asian (EAS) AF: 0.172 AC: 889 AN: 5182

South Asian (SAS) AF: 0.199 AC: 960 AN: 4814

European-Finnish (FIN) AF: 0.0808 AC: 857 AN: 10604

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0917 AC: 6234 AN: 68006

Other (OTH) AF: 0.123 AC: 259 AN: 2112

Alfa AF: 0.109 Hom.: 162

Bravo AF: 0.117

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4723003; hg19: chr7-30725741;