7-30687343-G-A

Variant names:

• chr7-30687343-G-A
• rs255097
• ENST00000348438.8:c.184+1848C>T

Variant summary

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

The ENST00000348438.8(CRHR2):​c.184+1848C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,804 control chromosomes in the GnomAD database, including 19,225 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 0.47 (19225 hom., cov: 30)
• Consequence: CRHR2 ENST00000348438.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716
• 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]

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 (NFE) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001202475.1	c.184+1848C>T		intron_variant	Intron 2 of 12		NP_001189404.1
CRHR2	NM_001202481.1	c.-166-728C>T		intron_variant	Intron 2 of 13		NP_001189410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000348438.8	c.184+1848C>T		intron_variant	Intron 2 of 12	1		ENSP00000340943.4
CRHR2	ENST00000445981.5	c.184+1848C>T		intron_variant	Intron 2 of 2	1		ENSP00000401241.1
CRHR2	ENST00000423776.1	n.185-728C>T		intron_variant	Intron 2 of 3	1		ENSP00000416620.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70908 AN: 151686 Hom.: 19224 Cov.: 30

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.467 AC: 70915 AN: 151804 Hom.: 19225 Cov.: 30 AF XY: 0.465 AC XY: 34507 AN XY: 74158

African (AFR) AF: 0.176 AC: 7282 AN: 41420

American (AMR) AF: 0.519 AC: 7922 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2266 AN: 3468

East Asian (EAS) AF: 0.439 AC: 2255 AN: 5132

South Asian (SAS) AF: 0.451 AC: 2158 AN: 4784

European-Finnish (FIN) AF: 0.577 AC: 6065 AN: 10506

Middle Eastern (MID) AF: 0.545 AC: 158 AN: 290

European-Non Finnish (NFE) AF: 0.607 AC: 41251 AN: 67934

Other (OTH) AF: 0.506 AC: 1068 AN: 2110

Alfa AF: 0.404 Hom.: 1763

Bravo AF: 0.450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.79
PhyloP100		-0.72
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: rs255097; hg19: chr7-30726959;