rs8192496

Variant names:

• chr7-30665489-G-A
• rs8192496
• NM_001883.5:c.425+41C>T

Variant summary

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

The NM_001883.5(CRHR2):​c.425+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,465,310 control chromosomes in the GnomAD database, including 339,123 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 0.62 (30174 hom., cov: 32)
  • Exomes 𝑓: 0.68 (308949 hom.)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 13 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.425+41C>T		intron_variant	Intron 4 of 11	ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.425+41C>T		intron_variant	Intron 4 of 11	1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94043 AN: 151958 Hom.: 30160 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.627

GnomAD2 exomes AF: 0.647 AC: 100711 AN: 155606 AF XY: 0.641

Gnomad AFR exome AF: 0.451

Gnomad AMR exome AF: 0.727

Gnomad ASJ exome AF: 0.716

Gnomad EAS exome AF: 0.482

Gnomad FIN exome AF: 0.713

Gnomad NFE exome AF: 0.702

Gnomad OTH exome AF: 0.666

GnomAD4 exome AF: 0.681 AC: 894087 AN: 1313234 Hom.: 308949 Cov.: 20 AF XY: 0.676 AC XY: 440504 AN XY: 651948

African (AFR) AF: 0.447 AC: 13313 AN: 29778

American (AMR) AF: 0.719 AC: 25544 AN: 35536

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 17724 AN: 24558

East Asian (EAS) AF: 0.414 AC: 14608 AN: 35282

South Asian (SAS) AF: 0.505 AC: 38946 AN: 77110

European-Finnish (FIN) AF: 0.711 AC: 35050 AN: 49282

Middle Eastern (MID) AF: 0.635 AC: 3497 AN: 5506

European-Non Finnish (NFE) AF: 0.708 AC: 709168 AN: 1000952

Other (OTH) AF: 0.656 AC: 36237 AN: 55230

GnomAD4 genome AF: 0.619 AC: 94087 AN: 152076 Hom.: 30174 Cov.: 32 AF XY: 0.617 AC XY: 45840 AN XY: 74304

African (AFR) AF: 0.453 AC: 18789 AN: 41472

American (AMR) AF: 0.677 AC: 10348 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2547 AN: 3472

East Asian (EAS) AF: 0.460 AC: 2372 AN: 5152

South Asian (SAS) AF: 0.497 AC: 2396 AN: 4818

European-Finnish (FIN) AF: 0.721 AC: 7628 AN: 10584

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47936 AN: 67972

Other (OTH) AF: 0.623 AC: 1313 AN: 2108

Alfa AF: 0.682 Hom.: 9405

Bravo AF: 0.610

Asia WGS AF: 0.467 AC: 1624 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.43
DANN	Benign	0.87
PhyloP100		-0.16
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: rs8192496; hg19: chr7-30705105; COSMIC: COSV59267639;