rs1003929

Variant names:

• chr7-30679433-T-C
• rs1003929
• NM_001883.5:c.229+2482A>G

Variant summary

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

The NM_001883.5(CRHR2):​c.229+2482A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,166 control chromosomes in the GnomAD database, including 57,502 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 0.87 (57502 hom., cov: 31)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.229+2482A>G		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.229+2482A>G		intron_variant	Intron 2 of 11	1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131561 AN: 152046 Hom.: 57446 Cov.: 31

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.867

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

GnomAD4 genome AF: 0.865 AC: 131675 AN: 152166 Hom.: 57502 Cov.: 31 AF XY: 0.859 AC XY: 63848 AN XY: 74370

African (AFR) AF: 0.967 AC: 40177 AN: 41532

American (AMR) AF: 0.851 AC: 13013 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3069 AN: 3472

East Asian (EAS) AF: 0.603 AC: 3110 AN: 5156

South Asian (SAS) AF: 0.731 AC: 3509 AN: 4802

European-Finnish (FIN) AF: 0.799 AC: 8463 AN: 10588

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57465 AN: 68010

Other (OTH) AF: 0.864 AC: 1827 AN: 2114

Alfa AF: 0.850 Hom.: 20730

Bravo AF: 0.875

Asia WGS AF: 0.718 AC: 2497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.32
PhyloP100		-0.72
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: rs1003929; hg19: chr7-30719049;