rs2135078

Variant names:

• chr5-76969643-G-A
• rs2135078
• ENST00000514258.1:n.311+6183G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-76969643-G-A
• chr5-76969643-G-C
• chr5-76969643-G-T

Variant summary

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

The ENST00000514258.1(CRHBP):​n.311+6183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,132 control chromosomes in the GnomAD database, including 11,391 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 0.38 (11391 hom., cov: 33)
• Consequence: CRHBP ENST00000514258.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

Genes affected

CRHBP (HGNC:2356): (corticotropin releasing hormone binding protein) Corticotropin-releasing hormone is a potent stimulator of synthesis and secretion of preopiomelanocortin-derived peptides. Although CRH concentrations in the human peripheral circulation are normally low, they increase throughout pregnancy and fall rapidly after parturition. Maternal plasma CRH probably originates from the placenta. Human plasma contains a CRH-binding protein which inactivates CRH and which may prevent inappropriate pituitary-adrenal stimulation in pregnancy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHBP	XR_948235.4	n.901+6183G>A		intron_variant	Intron 6 of 7
CRHBP	NM_001882.4	c.*758G>A		downstream_gene_variant		ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.*758G>A		downstream_gene_variant			XP_047272692.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000514258.1	n.311+6183G>A		intron_variant	Intron 2 of 3	3
CRHBP	ENST00000274368.9	c.*758G>A		downstream_gene_variant		1	NM_001882.4	ENSP00000274368.4

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58091 AN: 152014 Hom.: 11370 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.382 AC: 58150 AN: 152132 Hom.: 11391 Cov.: 33 AF XY: 0.387 AC XY: 28766 AN XY: 74354

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.380

Alfa AF: 0.261 Hom.: 838

Bravo AF: 0.374

Asia WGS AF: 0.473 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2135078; hg19: chr5-76265468;