rs12701020

Variant names:

• chr7-30655345-C-T
• rs12701020
• NM_001883.5:c.1053+235G>A

Variant summary

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

The NM_001883.5(CRHR2):​c.1053+235G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,210 control chromosomes in the GnomAD database, including 1,451 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 0.12 (1451 hom., cov: 33)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• 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]

LOC124901609 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.1053+235G>A		intron_variant	Intron 10 of 11	ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.1053+235G>A		intron_variant	Intron 10 of 11	1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17959 AN: 152092 Hom.: 1453 Cov.: 33

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.118 AC: 17947 AN: 152210 Hom.: 1451 Cov.: 33 AF XY: 0.120 AC XY: 8952 AN XY: 74428

African (AFR) AF: 0.0286 AC: 1188 AN: 41548

American (AMR) AF: 0.0966 AC: 1478 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 463 AN: 3472

East Asian (EAS) AF: 0.0384 AC: 199 AN: 5180

South Asian (SAS) AF: 0.127 AC: 613 AN: 4824

European-Finnish (FIN) AF: 0.247 AC: 2618 AN: 10588

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11065 AN: 67982

Other (OTH) AF: 0.130 AC: 275 AN: 2112

Alfa AF: 0.145 Hom.: 2873

Bravo AF: 0.102

Asia WGS AF: 0.0830 AC: 287 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	0.74
DANN	Benign	0.73
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12701020; hg19: chr7-30694961; COSMIC: COSV59268891;