rs8324

Positions:

• chr17-81843412-C-A
• chr17-81843412-C-G

Variant summary

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

The NM_000918.4(P4HB):​c.*600G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 399,174 control chromosomes in the GnomAD database, including 8,300 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 0.19 (3048 hom., cov: 33)
  • Exomes 𝑓: 0.20 (5252 hom.)
• Consequence: P4HB NM_000918.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P4HB	NM_000918.4	c.*600G>T		3_prime_UTR_variant	11/11	ENST00000331483.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P4HB	ENST00000331483.9	c.*600G>T		3_prime_UTR_variant	11/11	1	NM_000918.4	P1
	ENST00000576784.1	n.169+79C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29316 AN: 151956 Hom.: 3049 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.200 AC: 49377 AN: 247098 Hom.: 5252 Cov.: 0 AF XY: 0.199 AC XY: 24875 AN XY: 125242

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.193 AC: 29322 AN: 152076 Hom.: 3048 Cov.: 33 AF XY: 0.193 AC XY: 14334 AN XY: 74362

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.164

Alfa AF: 0.191 Hom.: 360

Bravo AF: 0.205

Asia WGS AF: 0.182 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.9
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8324; hg19: chr17-79801288;