7-30686085-A-G

Variant names:

• chr7-30686085-A-G
• rs4723002
• ENST00000348438.8:c.184+3106T>C

Variant summary

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

The ENST00000348438.8(CRHR2):​c.184+3106T>C 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 152,146 control chromosomes in the GnomAD database, including 1,175 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 (1175 hom., cov: 33)
• Consequence: CRHR2 ENST00000348438.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000348438.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	NM_001202475.1		c.184+3106T>C		intron	N/A	NP_001189404.1
	CRHR2	NM_001202481.1		c.61+304T>C		intron	N/A	NP_001189410.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	ENST00000348438.8	TSL:1	c.184+3106T>C		intron	N/A	ENSP00000340943.4
	CRHR2	ENST00000445981.5	TSL:1	c.184+3106T>C		intron	N/A	ENSP00000401241.1
	CRHR2	ENST00000423776.1	TSL:1	n.*216+304T>C		intron	N/A	ENSP00000416620.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17784 AN: 152028 Hom.: 1168 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0791

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.117 AC: 17807 AN: 152146 Hom.: 1175 Cov.: 33 AF XY: 0.117 AC XY: 8702 AN XY: 74378

African (AFR) AF: 0.168 AC: 6971 AN: 41510

American (AMR) AF: 0.0790 AC: 1208 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 339 AN: 3464

East Asian (EAS) AF: 0.172 AC: 889 AN: 5166

South Asian (SAS) AF: 0.199 AC: 958 AN: 4810

European-Finnish (FIN) AF: 0.0811 AC: 858 AN: 10578

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

European-Non Finnish (NFE) AF: 0.0919 AC: 6248 AN: 68016

Other (OTH) AF: 0.124 AC: 261 AN: 2112

Alfa AF: 0.102 Hom.: 1631

Bravo AF: 0.117

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.5
DANN	Benign	0.73
PhyloP100		-0.24
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: rs4723002; hg19: chr7-30725701;