7-30673085-C-G

Variant names:

• chr7-30673085-C-G
• rs1076292
• NM_001883.5:c.230-5772G>C

Variant summary

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

The NM_001883.5(CRHR2):​c.230-5772G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,134 control chromosomes in the GnomAD database, including 21,947 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 0.50 (21947 hom., cov: 32)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774
• Publications: 15 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.230-5772G>C		intron_variant	Intron 2 of 11	ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.230-5772G>C		intron_variant	Intron 2 of 11	1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75907 AN: 152014 Hom.: 21949 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.499 AC: 75911 AN: 152134 Hom.: 21947 Cov.: 32 AF XY: 0.497 AC XY: 36947 AN XY: 74362

African (AFR) AF: 0.193 AC: 8008 AN: 41506

American (AMR) AF: 0.550 AC: 8416 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2476 AN: 3472

East Asian (EAS) AF: 0.446 AC: 2303 AN: 5164

South Asian (SAS) AF: 0.463 AC: 2228 AN: 4816

European-Finnish (FIN) AF: 0.627 AC: 6639 AN: 10594

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44025 AN: 67970

Other (OTH) AF: 0.538 AC: 1137 AN: 2112

Alfa AF: 0.442 Hom.: 1468

Bravo AF: 0.479

Asia WGS AF: 0.418 AC: 1455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1076292; hg19: chr7-30712701;