chr7-30660356-G-C

Position:

• chr7-30660356-G-C

Variant summary

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

The NM_001883.5(CRHR2):​c.831+217C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,310 control chromosomes in the GnomAD database, including 54,794 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 0.85 (54794 hom., cov: 35)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR2	NM_001883.5	c.831+217C>G		intron_variant		ENST00000471646.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR2	ENST00000471646.6	c.831+217C>G		intron_variant		1	NM_001883.5	P1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128632 AN: 152190 Hom.: 54742 Cov.: 35

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.852

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

GnomAD4 genome AF: 0.845 AC: 128742 AN: 152310 Hom.: 54794 Cov.: 35 AF XY: 0.839 AC XY: 62479 AN XY: 74454

Gnomad4 AFR AF: 0.933

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.851

Alfa AF: 0.841 Hom.: 6701

Bravo AF: 0.855

Asia WGS AF: 0.708 AC: 2462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.76

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: rs2270007; hg19: chr7-30699972;