7-30654644-C-T

Variant names:

• chr7-30654644-C-T
• rs3779250
• NM_001883.5:c.1095+395G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 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]

LOC124901609 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001883.5. 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_001883.5	MANE Select	c.1095+395G>A		intron	N/A	NP_001874.2
	CRHR2	NM_001202475.1		c.1176+395G>A		intron	N/A	NP_001189404.1
	CRHR2	NM_001202482.2		c.1092+395G>A		intron	N/A	NP_001189411.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	ENST00000471646.6	TSL:1 MANE Select	c.1095+395G>A		intron	N/A	ENSP00000418722.1
	CRHR2	ENST00000348438.8	TSL:1	c.1176+395G>A		intron	N/A	ENSP00000340943.4
	CRHR2	ENST00000506074.6	TSL:1	c.*42+54G>A		intron	N/A	ENSP00000426498.3

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

African (AFR) AF: 0.118 AC: 3669 AN: 31084

American (AMR) AF: 0.551 AC: 19408 AN: 35250

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 16586 AN: 24792

East Asian (EAS) AF: 0.443 AC: 15699 AN: 35462

South Asian (SAS) AF: 0.423 AC: 33001 AN: 78056

European-Finnish (FIN) AF: 0.640 AC: 21573 AN: 33684

Middle Eastern (MID) AF: 0.548 AC: 3087 AN: 5636

European-Non Finnish (NFE) AF: 0.651 AC: 692629 AN: 1063258

Other (OTH) AF: 0.577 AC: 32910 AN: 57036

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

African (AFR) AF: 0.140 AC: 5829 AN: 41520

American (AMR) AF: 0.531 AC: 8125 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2366 AN: 3466

East Asian (EAS) AF: 0.471 AC: 2430 AN: 5156

South Asian (SAS) AF: 0.419 AC: 2018 AN: 4816

European-Finnish (FIN) AF: 0.643 AC: 6815 AN: 10596

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44041 AN: 67970

Other (OTH) AF: 0.513 AC: 1084 AN: 2114

Alfa AF: 0.587 Hom.: 20224

Bravo AF: 0.461

Asia WGS AF: 0.410 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.86
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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