7-30657741-T-A

Variant names:

• chr7-30657741-T-A
• rs975537
• NM_001883.5:c.832-1729A>T

Variant summary

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

The NM_001883.5(CRHR2):​c.832-1729A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,128 control chromosomes in the GnomAD database, including 48,936 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 0.80 (48936 hom., cov: 31)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412
• Publications: 14 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 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.832-1729A>T		intron	N/A	NP_001874.2
	CRHR2	NM_001202475.1		c.913-1729A>T		intron	N/A	NP_001189404.1
	CRHR2	NM_001202482.2		c.829-1729A>T		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.832-1729A>T		intron	N/A	ENSP00000418722.1
	CRHR2	ENST00000348438.8	TSL:1	c.913-1729A>T		intron	N/A	ENSP00000340943.4
	CRHR2	ENST00000506074.6	TSL:1	c.832-1729A>T		intron	N/A	ENSP00000426498.3

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121327 AN: 152010 Hom.: 48895 Cov.: 31

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.798 AC: 121423 AN: 152128 Hom.: 48936 Cov.: 31 AF XY: 0.790 AC XY: 58750 AN XY: 74366

African (AFR) AF: 0.906 AC: 37626 AN: 41516

American (AMR) AF: 0.734 AC: 11225 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2856 AN: 3470

East Asian (EAS) AF: 0.655 AC: 3376 AN: 5154

South Asian (SAS) AF: 0.636 AC: 3064 AN: 4820

European-Finnish (FIN) AF: 0.719 AC: 7610 AN: 10582

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53009 AN: 67972

Other (OTH) AF: 0.810 AC: 1712 AN: 2114

Alfa AF: 0.709 Hom.: 2033

Bravo AF: 0.807

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.74
PhyloP100		0.41
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: rs975537; hg19: chr7-30697357; COSMIC: COSV59263841;