7-30689292-A-T

Variant names:

• chr7-30689292-A-T
• rs255100
• ENST00000348438.8:c.91-8T>A

Variant summary

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

The ENST00000348438.8(CRHR2):​c.91-8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,548,616 control chromosomes in the GnomAD database, including 260,049 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (18845 hom., cov: 33)
  • Exomes 𝑓: 0.58 (241204 hom.)
• Consequence: CRHR2 ENST00000348438.8 splice_region, intron
• Scores: Splicing: ADA: 0.01359
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 15 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000348438.8. 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_001202475.1		c.91-8T>A		splice_region intron	N/A	NP_001189404.1
	CRHR2	NM_001202481.1		c.-260-8T>A		splice_region intron	N/A	NP_001189410.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRHR2	ENST00000348438.8	TSL:1	c.91-8T>A		splice_region intron	N/A	ENSP00000340943.4
	CRHR2	ENST00000445981.5	TSL:1	c.91-8T>A		splice_region intron	N/A	ENSP00000401241.1
	CRHR2	ENST00000423776.1	TSL:1	n.91-8T>A		splice_region intron	N/A	ENSP00000416620.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68944 AN: 151994 Hom.: 18845 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.496

GnomAD2 exomes AF: 0.533 AC: 78072 AN: 146468 AF XY: 0.534

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.539

Gnomad ASJ exome AF: 0.633

Gnomad EAS exome AF: 0.461

Gnomad FIN exome AF: 0.561

Gnomad NFE exome AF: 0.606

Gnomad OTH exome AF: 0.535

GnomAD4 exome AF: 0.580 AC: 810314 AN: 1396504 Hom.: 241204 Cov.: 34 AF XY: 0.577 AC XY: 397477 AN XY: 688844

African (AFR) AF: 0.113 AC: 3573 AN: 31560

American (AMR) AF: 0.529 AC: 18886 AN: 35678

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 15906 AN: 25168

East Asian (EAS) AF: 0.405 AC: 14451 AN: 35716

South Asian (SAS) AF: 0.451 AC: 35704 AN: 79196

European-Finnish (FIN) AF: 0.561 AC: 26879 AN: 47930

Middle Eastern (MID) AF: 0.517 AC: 2928 AN: 5660

European-Non Finnish (NFE) AF: 0.613 AC: 660362 AN: 1077692

Other (OTH) AF: 0.546 AC: 31625 AN: 57904

GnomAD4 genome AF: 0.453 AC: 68949 AN: 152112 Hom.: 18845 Cov.: 33 AF XY: 0.452 AC XY: 33628 AN XY: 74334

African (AFR) AF: 0.131 AC: 5452 AN: 41526

American (AMR) AF: 0.516 AC: 7878 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2257 AN: 3472

East Asian (EAS) AF: 0.446 AC: 2294 AN: 5148

South Asian (SAS) AF: 0.449 AC: 2168 AN: 4824

European-Finnish (FIN) AF: 0.571 AC: 6048 AN: 10586

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41157 AN: 67958

Other (OTH) AF: 0.493 AC: 1042 AN: 2112

Alfa AF: 0.558 Hom.: 7526

Bravo AF: 0.435

Asia WGS AF: 0.411 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.1
DANN	Benign	0.71
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.014
dbscSNV1_RF	Benign	0.066

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs255100; hg19: chr7-30728908; COSMIC: COSV59263807;