7-30655586-C-T

Variant names:

• chr7-30655586-C-T
• rs2240403
• NM_001883.5:c.1047G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001883.5(CRHR2):​c.1047G>A​(p.Ser349Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 1,611,880 control chromosomes in the GnomAD database, including 8,740 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 0.099 (834 hom., cov: 33)
  • Exomes 𝑓: 0.097 (7906 hom.)
• Consequence: CRHR2 NM_001883.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 19 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-2.94 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.1047G>A	p.Ser349Ser	synonymous_variant	Exon 10 of 12	ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.1047G>A	p.Ser349Ser	synonymous_variant	Exon 10 of 12	1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15086 AN: 152142 Hom.: 831 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0940

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0868

Gnomad OTH AF: 0.126

GnomAD2 exomes AF: 0.107 AC: 26593 AN: 249494 AF XY: 0.110

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.0754

Gnomad ASJ exome AF: 0.102

Gnomad EAS exome AF: 0.162

Gnomad FIN exome AF: 0.0623

Gnomad NFE exome AF: 0.0920

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.0967 AC: 141162 AN: 1459618 Hom.: 7906 Cov.: 33 AF XY: 0.0994 AC XY: 72176 AN XY: 726016

African (AFR) AF: 0.110 AC: 3667 AN: 33462

American (AMR) AF: 0.0766 AC: 3414 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 2597 AN: 25932

East Asian (EAS) AF: 0.192 AC: 7619 AN: 39688

South Asian (SAS) AF: 0.189 AC: 16194 AN: 85886

European-Finnish (FIN) AF: 0.0622 AC: 3316 AN: 53300

Middle Eastern (MID) AF: 0.149 AC: 859 AN: 5746

European-Non Finnish (NFE) AF: 0.0873 AC: 96947 AN: 1110706

Other (OTH) AF: 0.109 AC: 6549 AN: 60308

GnomAD4 genome AF: 0.0992 AC: 15099 AN: 152262 Hom.: 834 Cov.: 33 AF XY: 0.100 AC XY: 7468 AN XY: 74440

African (AFR) AF: 0.110 AC: 4584 AN: 41554

American (AMR) AF: 0.0938 AC: 1437 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 325 AN: 3472

East Asian (EAS) AF: 0.181 AC: 935 AN: 5172

South Asian (SAS) AF: 0.197 AC: 951 AN: 4822

European-Finnish (FIN) AF: 0.0611 AC: 648 AN: 10608

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0867 AC: 5899 AN: 68004

Other (OTH) AF: 0.130 AC: 275 AN: 2112

Alfa AF: 0.0812 Hom.: 386

Bravo AF: 0.102

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.68
DANN	Benign	0.71
PhyloP100		-2.9
Mutation Taster		=98/2	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: rs2240403; hg19: chr7-30695202; COSMIC: COSV59265338;