7-30690056-A-C

Position:

• chr7-30690056-A-C

Variant summary

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

The ENST00000348438.8(CRHR2):​c.91-772T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0813 in 152,278 control chromosomes in the GnomAD database, including 568 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 0.081 (568 hom., cov: 33)
• Consequence: CRHR2 ENST00000348438.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.622

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR2	NM_001202475.1	c.91-772T>G		intron_variant			NP_001189404.1
CRHR2	NM_001202481.1	c.-260-772T>G		intron_variant			NP_001189410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000348438.8	c.91-772T>G		intron_variant		1		ENSP00000340943
CRHR2	ENST00000445981.5	c.91-772T>G		intron_variant		1		ENSP00000401241
CRHR2	ENST00000423776.1	c.91-772T>G		intron_variant, NMD_transcript_variant		1		ENSP00000416620

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12366 AN: 152160 Hom.: 564 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0380

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0521

Gnomad FIN AF: 0.0904

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0696

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0813 AC: 12380 AN: 152278 Hom.: 568 Cov.: 33 AF XY: 0.0820 AC XY: 6105 AN XY: 74464

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0380

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0517

Gnomad4 FIN AF: 0.0904

Gnomad4 NFE AF: 0.0696

Gnomad4 OTH AF: 0.0672

Alfa AF: 0.0670 Hom.: 235

Bravo AF: 0.0855

Asia WGS AF: 0.0340 AC: 118 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	0.67
DANN	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17159371; hg19: chr7-30729672;