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. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.426 AC: 17676 AN: 41486

American (AMR) AF: 0.335 AC: 5126 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1300 AN: 3472

East Asian (EAS) AF: 0.567 AC: 2933 AN: 5174

South Asian (SAS) AF: 0.435 AC: 2100 AN: 4824

European-Finnish (FIN) AF: 0.439 AC: 4648 AN: 10576

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23112 AN: 67984

Other (OTH) AF: 0.380 AC: 805 AN: 2116

Alfa AF: 0.267 Hom.: 905

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
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs2135078; hg19: chr5-76265468;