17-81852766-A-G

Position:

• chr17-81852766-A-G

Variant summary

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

The ENST00000331483.9(P4HB):​c.624+2376T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,228 control chromosomes in the GnomAD database, including 4,340 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 0.23 (4340 hom., cov: 33)
• Consequence: P4HB ENST00000331483.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.966

Genes affected

P4HB (HGNC:8548): (prolyl 4-hydroxylase subunit beta) This gene encodes the beta subunit of prolyl 4-hydroxylase, a highly abundant multifunctional enzyme that belongs to the protein disulfide isomerase family. When present as a tetramer consisting of two alpha and two beta subunits, this enzyme is involved in hydroxylation of prolyl residues in preprocollagen. This enzyme is also a disulfide isomerase containing two thioredoxin domains that catalyze the formation, breakage and rearrangement of disulfide bonds. Other known functions include its ability to act as a chaperone that inhibits aggregation of misfolded proteins in a concentration-dependent manner, its ability to bind thyroid hormone, its role in both the influx and efflux of S-nitrosothiol-bound nitric oxide, and its function as a subunit of the microsomal triglyceride transfer protein complex. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P4HB	NM_000918.4	c.624+2376T>C		intron_variant		ENST00000331483.9	NP_000909.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P4HB	ENST00000331483.9	c.624+2376T>C		intron_variant		1	NM_000918.4	ENSP00000327801	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35135 AN: 152110 Hom.: 4337 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.231 AC: 35162 AN: 152228 Hom.: 4340 Cov.: 33 AF XY: 0.230 AC XY: 17095 AN XY: 74444

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.193

Alfa AF: 0.214 Hom.: 531

Bravo AF: 0.248

Asia WGS AF: 0.202 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.38
DANN	Benign	0.19

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: rs876017; hg19: chr17-79810642;