rs975537

Positions:

• chr7-30657741-T-A
• chr7-30657741-T-C
• chr7-30657741-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001883.5(CRHR2):​c.832-1729A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,128 control chromosomes in the GnomAD database, including 48,936 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 0.80 (48936 hom., cov: 31)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRHR2	NM_001883.5	c.832-1729A>T		intron_variant		ENST00000471646.6
LOC124901609	XR_007060276.1	n.3945T>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRHR2	ENST00000471646.6	c.832-1729A>T		intron_variant		1	NM_001883.5	P1

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121327 AN: 152010 Hom.: 48895 Cov.: 31

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.798 AC: 121423 AN: 152128 Hom.: 48936 Cov.: 31 AF XY: 0.790 AC XY: 58750 AN XY: 74366

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.823

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.810

Alfa AF: 0.709 Hom.: 2033

Bravo AF: 0.807

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs975537; hg19: chr7-30697357; COSMIC: COSV59263841;