7-30687343-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000348438.8(CRHR2):​c.184+1848C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,918 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001202475.1	c.184+1848C>A		intron_variant	Intron 2 of 12		NP_001189404.1
CRHR2	NM_001202481.1	c.-166-728C>A		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>A		intron_variant	Intron 2 of 12	1		ENSP00000340943.4
CRHR2	ENST00000445981.5	c.184+1848C>A		intron_variant	Intron 2 of 2	1		ENSP00000401241.1
CRHR2	ENST00000423776.1	n.185-728C>A		intron_variant	Intron 2 of 3	1		ENSP00000416620.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151798 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151918 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74228

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.000418 AC: 2 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 1763

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.70
PhyloP100		-0.72

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;