chr7-30682880-G-C

Variant names:

• chr7-30682880-G-C
• rs6967702
• ENST00000348438.8:c.185-840C>G

Variant summary

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

The ENST00000348438.8(CRHR2):​c.185-840C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 152,366 control chromosomes in the GnomAD database, including 190 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 0.028 (190 hom., cov: 33)
• Consequence: CRHR2 ENST00000348438.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 4 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]

LOC124901608 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901608	XR_007060275.1	n.262G>C		non_coding_transcript_exon_variant	Exon 1 of 2
CRHR2	NM_001202475.1	c.185-840C>G		intron_variant	Intron 2 of 12		NP_001189404.1
CRHR2	NM_001202481.1	c.62-840C>G		intron_variant	Intron 3 of 13		NP_001189410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000348438.8	c.185-840C>G		intron_variant	Intron 2 of 12	1		ENSP00000340943.4
CRHR2	ENST00000445981.5	c.185-548C>G		intron_variant	Intron 2 of 2	1		ENSP00000401241.1
CRHR2	ENST00000423776.1	n.*217-548C>G		intron_variant	Intron 3 of 3	1		ENSP00000416620.1

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 4182 AN: 152248 Hom.: 190 Cov.: 33

Gnomad AFR AF: 0.0954

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0275 AC: 4194 AN: 152366 Hom.: 190 Cov.: 33 AF XY: 0.0264 AC XY: 1970 AN XY: 74516

African (AFR) AF: 0.0954 AC: 3967 AN: 41586

American (AMR) AF: 0.0104 AC: 159 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68034

Other (OTH) AF: 0.0194 AC: 41 AN: 2116

Alfa AF: 0.0206 Hom.: 12

Bravo AF: 0.0313

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.2
DANN	Benign	0.68
PhyloP100		0.34
PromoterAI		0.0073	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6967702; hg19: chr7-30722496;