7-30664543-A-T

Position:

• chr7-30664543-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001883.5(CRHR2):​c.543+527T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 152,034 control chromosomes in the GnomAD database, including 26,260 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 0.55 (26260 hom., cov: 31)
• Consequence: CRHR2 NM_001883.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR2	NM_001883.5	c.543+527T>A		intron_variant		ENST00000471646.6	NP_001874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR2	ENST00000471646.6	c.543+527T>A		intron_variant		1	NM_001883.5	ENSP00000418722.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83833 AN: 151916 Hom.: 26256 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.551 AC: 83845 AN: 152034 Hom.: 26260 Cov.: 31 AF XY: 0.552 AC XY: 41019 AN XY: 74322

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.574

Alfa AF: 0.618 Hom.: 3865

Bravo AF: 0.534

Asia WGS AF: 0.451 AC: 1568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs929377; hg19: chr7-30704159;