7-30692491-T-C

Variant names:

• chr7-30692491-T-C
• rs255105
• ENST00000348438.8:c.91-3207A>G

Variant summary

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

The ENST00000348438.8(CRHR2):​c.91-3207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,070 control chromosomes in the GnomAD database, including 22,836 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 0.51 (22836 hom., cov: 32)
• Consequence: CRHR2 ENST00000348438.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001202475.1	c.91-3207A>G		intron_variant	Intron 1 of 12		NP_001189404.1
CRHR2	NM_001202481.1	c.-260-3207A>G		intron_variant	Intron 1 of 13		NP_001189410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000348438.8	c.91-3207A>G		intron_variant	Intron 1 of 12	1		ENSP00000340943.4
CRHR2	ENST00000445981.5	c.91-3207A>G		intron_variant	Intron 1 of 2	1		ENSP00000401241.1
CRHR2	ENST00000423776.1	n.91-3207A>G		intron_variant	Intron 1 of 3	1		ENSP00000416620.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76951 AN: 151952 Hom.: 22843 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.506 AC: 76948 AN: 152070 Hom.: 22836 Cov.: 32 AF XY: 0.506 AC XY: 37633 AN XY: 74354

African (AFR) AF: 0.179 AC: 7442 AN: 41488

American (AMR) AF: 0.544 AC: 8310 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2373 AN: 3470

East Asian (EAS) AF: 0.576 AC: 2956 AN: 5134

South Asian (SAS) AF: 0.420 AC: 2024 AN: 4822

European-Finnish (FIN) AF: 0.675 AC: 7132 AN: 10570

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44839 AN: 67990

Other (OTH) AF: 0.544 AC: 1147 AN: 2108

Alfa AF: 0.580 Hom.: 9994

Bravo AF: 0.487

Asia WGS AF: 0.439 AC: 1528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.39
PhyloP100		-0.26
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: rs255105; hg19: chr7-30732107;