NM_001882.4:c.223G>T

Variant names:

• chr5-76954076-G-T
• rs377064988
• NM_001882.4:c.223G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001882.4(CRHBP):​c.223G>T​(p.Asp75Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRHBP NM_001882.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRHBP	NM_001882.4	c.223G>T	p.Asp75Tyr	missense_variant	Exon 3 of 7	ENST00000274368.9	NP_001873.2
CRHBP	XM_047416736.1	c.37G>T	p.Asp13Tyr	missense_variant	Exon 2 of 6		XP_047272692.1
CRHBP	XR_948235.4	n.313G>T		non_coding_transcript_exon_variant	Exon 3 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRHBP	ENST00000274368.9	c.223G>T	p.Asp75Tyr	missense_variant	Exon 3 of 7	1	NM_001882.4	ENSP00000274368.4
CRHBP	ENST00000506501.1	c.223G>T	p.Asp75Tyr	missense_variant	Exon 3 of 5	1		ENSP00000426097.1
CRHBP	ENST00000512446.1	n.326G>T		non_coding_transcript_exon_variant	Exon 2 of 4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461588 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727118

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.96	D;P
Vest4		0.46
MutPred		0.64		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.28
MPC		1.5
ClinPred		0.98	D
GERP RS		3.1
Varity_R		0.40
gMVP		0.62

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: rs377064988; hg19: chr5-76249901;