rs7812133

Variant names:

• chr7-30655790-G-A
• rs7812133
• NM_001883.5:c.918-75C>T

Variant summary

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

The NM_001202475.1(CRHR2):​c.999-75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,591,760 control chromosomes in the GnomAD database, including 3,875 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 0.10 (1611 hom., cov: 33)
  • Exomes 𝑓: 0.040 (2264 hom.)
• Consequence: CRHR2 NM_001202475.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202475.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	NM_001883.5	MANE Select	c.918-75C>T		intron	N/A	NP_001874.2
	CRHR2	NM_001202475.1		c.999-75C>T		intron	N/A	NP_001189404.1
	CRHR2	NM_001202482.2		c.915-75C>T		intron	N/A	NP_001189411.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	ENST00000471646.6	TSL:1 MANE Select	c.918-75C>T		intron	N/A	ENSP00000418722.1
	CRHR2	ENST00000348438.8	TSL:1	c.999-75C>T		intron	N/A	ENSP00000340943.4
	CRHR2	ENST00000506074.6	TSL:1	c.918-75C>T		intron	N/A	ENSP00000426498.3

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15201 AN: 152052 Hom.: 1600 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0843

GnomAD4 exome AF: 0.0399 AC: 57488 AN: 1439592 Hom.: 2264 Cov.: 31 AF XY: 0.0383 AC XY: 27366 AN XY: 713966

African (AFR) AF: 0.283 AC: 9330 AN: 33016

American (AMR) AF: 0.0410 AC: 1779 AN: 43362

Ashkenazi Jewish (ASJ) AF: 0.0284 AC: 700 AN: 24620

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39476

South Asian (SAS) AF: 0.00843 AC: 703 AN: 83388

European-Finnish (FIN) AF: 0.0118 AC: 613 AN: 52076

Middle Eastern (MID) AF: 0.0493 AC: 268 AN: 5438

European-Non Finnish (NFE) AF: 0.0374 AC: 41097 AN: 1098868

Other (OTH) AF: 0.0504 AC: 2992 AN: 59348

GnomAD4 genome AF: 0.100 AC: 15237 AN: 152168 Hom.: 1611 Cov.: 33 AF XY: 0.0965 AC XY: 7181 AN XY: 74402

African (AFR) AF: 0.271 AC: 11242 AN: 41462

American (AMR) AF: 0.0636 AC: 974 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5160

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4828

European-Finnish (FIN) AF: 0.0105 AC: 112 AN: 10630

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0357 AC: 2430 AN: 67990

Other (OTH) AF: 0.0834 AC: 176 AN: 2110

Alfa AF: 0.0635 Hom.: 1022

Bravo AF: 0.113

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.31
DANN	Benign	0.53
PhyloP100		-0.46
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: rs7812133; hg19: chr7-30695406;