7-30654644-C-T

Position:

• chr7-30654644-C-T

Variant summary

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

The NM_001883.5(CRHR2):​c.1095+395G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,516,390 control chromosomes in the GnomAD database, including 286,827 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 0.48 (21456 hom., cov: 33)
  • Exomes 𝑓: 0.61 (265371 hom.)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.1095+395G>A		intron_variant		ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.1095+395G>A		intron_variant		1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73428 AN: 152012 Hom.: 21461 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.615 AC: 838562 AN: 1364258 Hom.: 265371 AF XY: 0.610 AC XY: 410479 AN XY: 672648

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.551

Gnomad4 ASJ exome AF: 0.669

Gnomad4 EAS exome AF: 0.443

Gnomad4 SAS exome AF: 0.423

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.651

Gnomad4 OTH exome AF: 0.577

GnomAD4 genome AF: 0.483 AC: 73421 AN: 152132 Hom.: 21456 Cov.: 33 AF XY: 0.480 AC XY: 35723 AN XY: 74374

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.513

Alfa AF: 0.611 Hom.: 10751

Bravo AF: 0.461

Asia WGS AF: 0.410 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.86

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: rs3779250; hg19: chr7-30694260; COSMIC: COSV59265221;