chr7-30688836-C-T

Variant names:

• chr7-30688836-C-T
• rs917195
• ENST00000462882.1:n.453G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000462882.1(CRHR2):​n.453G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 466,224 control chromosomes in the GnomAD database, including 26,213 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 0.37 (14656 hom., cov: 34)
  • Exomes 𝑓: 0.25 (11557 hom.)
• Consequence: CRHR2 ENST00000462882.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 18 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000462882.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	NM_001202475.1		c.184+355G>A		intron	N/A	NP_001189404.1
	CRHR2	NM_001202481.1		c.-167+355G>A		intron	N/A	NP_001189410.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	ENST00000462882.1	TSL:1	n.453G>A		non_coding_transcript_exon	Exon 3 of 4
	CRHR2	ENST00000348438.8	TSL:1	c.184+355G>A		intron	N/A	ENSP00000340943.4
	CRHR2	ENST00000445981.5	TSL:1	c.184+355G>A		intron	N/A	ENSP00000401241.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56931 AN: 151980 Hom.: 14618 Cov.: 34

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.338

GnomAD2 exomes AF: 0.265 AC: 35472 AN: 133778 AF XY: 0.258

Gnomad AFR exome AF: 0.762

Gnomad AMR exome AF: 0.287

Gnomad ASJ exome AF: 0.226

Gnomad EAS exome AF: 0.156

Gnomad FIN exome AF: 0.187

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.253 AC: 79616 AN: 314126 Hom.: 11557 Cov.: 0 AF XY: 0.252 AC XY: 44849 AN XY: 178120

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.743 AC: 6723 AN: 9050

American (AMR) AF: 0.287 AC: 7878 AN: 27428

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 2579 AN: 11232

East Asian (EAS) AF: 0.166 AC: 1661 AN: 9998

South Asian (SAS) AF: 0.272 AC: 16200 AN: 59664

European-Finnish (FIN) AF: 0.192 AC: 2535 AN: 13196

Middle Eastern (MID) AF: 0.293 AC: 834 AN: 2848

European-Non Finnish (NFE) AF: 0.224 AC: 37194 AN: 165684

Other (OTH) AF: 0.267 AC: 4012 AN: 15026

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.375 AC: 57032 AN: 152098 Hom.: 14656 Cov.: 34 AF XY: 0.369 AC XY: 27431 AN XY: 74392

African (AFR) AF: 0.743 AC: 30785 AN: 41436

American (AMR) AF: 0.304 AC: 4646 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3472

East Asian (EAS) AF: 0.176 AC: 913 AN: 5178

South Asian (SAS) AF: 0.274 AC: 1319 AN: 4820

European-Finnish (FIN) AF: 0.189 AC: 2009 AN: 10612

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15515 AN: 67972

Other (OTH) AF: 0.339 AC: 716 AN: 2114

Alfa AF: 0.306 Hom.: 2660

Bravo AF: 0.402

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		-0.031
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: rs917195; hg19: chr7-30728452; COSMIC: COSV59264279;