rs1053989

Variant names:

• chr5-76969210-C-A
• rs1053989
• NM_001882.4:c.*325C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-76969210-C-A
• chr5-76969210-C-G
• chr5-76969210-C-T

Variant summary

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

The NM_001882.4(CRHBP):​c.*325C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 203,854 control chromosomes in the GnomAD database, including 25,328 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 0.50 (20587 hom., cov: 33)
  • Exomes 𝑓: 0.42 (4741 hom.)
• Consequence: CRHBP NM_001882.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHBP	NM_001882.4	c.*325C>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.*325C>A		3_prime_UTR_variant	Exon 6 of 6		XP_047272692.1
CRHBP	XR_948235.4	n.901+5750C>A		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.*325C>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_001882.4	ENSP00000274368.4
CRHBP	ENST00000514258.1	n.311+5750C>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75366 AN: 151942 Hom.: 20536 Cov.: 33

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.488

GnomAD4 exome AF: 0.418 AC: 21631 AN: 51794 Hom.: 4741 Cov.: 0 AF XY: 0.414 AC XY: 10760 AN XY: 25996

African (AFR) AF: 0.727 AC: 1487 AN: 2044

American (AMR) AF: 0.378 AC: 649 AN: 1718

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1034 AN: 2246

East Asian (EAS) AF: 0.582 AC: 2225 AN: 3820

South Asian (SAS) AF: 0.443 AC: 433 AN: 978

European-Finnish (FIN) AF: 0.449 AC: 1384 AN: 3082

Middle Eastern (MID) AF: 0.503 AC: 145 AN: 288

European-Non Finnish (NFE) AF: 0.374 AC: 12738 AN: 34072

Other (OTH) AF: 0.433 AC: 1536 AN: 3546

GnomAD4 genome AF: 0.496 AC: 75465 AN: 152060 Hom.: 20587 Cov.: 33 AF XY: 0.497 AC XY: 36894 AN XY: 74300

African (AFR) AF: 0.728 AC: 30221 AN: 41510

American (AMR) AF: 0.400 AC: 6115 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1621 AN: 3462

East Asian (EAS) AF: 0.568 AC: 2938 AN: 5172

South Asian (SAS) AF: 0.464 AC: 2239 AN: 4824

European-Finnish (FIN) AF: 0.464 AC: 4884 AN: 10530

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25869 AN: 67974

Other (OTH) AF: 0.491 AC: 1037 AN: 2112

Alfa AF: 0.422 Hom.: 40254

Bravo AF: 0.502

Asia WGS AF: 0.505 AC: 1756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.49
PhyloP100		1.5
Mutation Taster		=100/0	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: rs1053989; hg19: chr5-76265035;