7-30677027-T-C

Position:

• chr7-30677027-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001883.5(CRHR2):​c.229+4888A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,958 control chromosomes in the GnomAD database, including 15,534 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 0.38 (15534 hom., cov: 32)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR2	NM_001883.5	c.229+4888A>G		intron_variant		ENST00000471646.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR2	ENST00000471646.6	c.229+4888A>G		intron_variant		1	NM_001883.5	P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58334 AN: 151836 Hom.: 15494 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.385 AC: 58443 AN: 151958 Hom.: 15534 Cov.: 32 AF XY: 0.380 AC XY: 28215 AN XY: 74242

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.342

Alfa AF: 0.245 Hom.: 6869

Bravo AF: 0.410

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.016
DANN	Benign	0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs2267716; hg19: chr7-30716643;