7-30691548-A-T

Variant names:

• chr7-30691548-A-T
• rs255102
• ENST00000348438.8:c.91-2264T>A

Variant summary

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

The ENST00000348438.8(CRHR2):​c.91-2264T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,110 control chromosomes in the GnomAD database, including 12,391 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 0.39 (12391 hom., cov: 33)
• Consequence: CRHR2 ENST00000348438.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.674
• Publications: 10 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 (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000348438.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	NM_001202475.1		c.91-2264T>A		intron	N/A	NP_001189404.1
	CRHR2	NM_001202481.1		c.-260-2264T>A		intron	N/A	NP_001189410.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	ENST00000348438.8	TSL:1	c.91-2264T>A		intron	N/A	ENSP00000340943.4
	CRHR2	ENST00000445981.5	TSL:1	c.91-2264T>A		intron	N/A	ENSP00000401241.1
	CRHR2	ENST00000423776.1	TSL:1	n.91-2264T>A		intron	N/A	ENSP00000416620.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59715 AN: 151992 Hom.: 12380 Cov.: 33

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.393 AC: 59746 AN: 152110 Hom.: 12391 Cov.: 33 AF XY: 0.392 AC XY: 29127 AN XY: 74372

African (AFR) AF: 0.542 AC: 22468 AN: 41478

American (AMR) AF: 0.363 AC: 5553 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1094 AN: 3464

East Asian (EAS) AF: 0.197 AC: 1018 AN: 5174

South Asian (SAS) AF: 0.349 AC: 1686 AN: 4826

European-Finnish (FIN) AF: 0.386 AC: 4083 AN: 10578

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.333 AC: 22632 AN: 67994

Other (OTH) AF: 0.362 AC: 763 AN: 2108

Alfa AF: 0.383 Hom.: 1464

Bravo AF: 0.398

Asia WGS AF: 0.328 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.75
PhyloP100		0.67
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: rs255102; hg19: chr7-30731164;