chr17-81844179-G-A

Position:

• chr17-81844179-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000918.4(P4HB):​c.1447-87C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 956,842 control chromosomes in the GnomAD database, including 292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (191 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (101 hom.)
• Consequence: P4HB NM_000918.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.440

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-81844179-G-A is Benign according to our data. Variant chr17-81844179-G-A is described in ClinVar as [Benign]. Clinvar id is 1272512.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P4HB	NM_000918.4	c.1447-87C>T		intron_variant		ENST00000331483.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P4HB	ENST00000331483.9	c.1447-87C>T		intron_variant		1	NM_000918.4	P1

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4120 AN: 152168 Hom.: 188 Cov.: 33

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00923

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.00329 AC: 2645 AN: 804556 Hom.: 101 AF XY: 0.00269 AC XY: 1144 AN XY: 425878

Gnomad4 AFR exome AF: 0.0937

Gnomad4 AMR exome AF: 0.00544

Gnomad4 ASJ exome AF: 0.00382

Gnomad4 EAS exome AF: 0.0000272

Gnomad4 SAS exome AF: 0.000260

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000164

Gnomad4 OTH exome AF: 0.00707

GnomAD4 genome AF: 0.0271 AC: 4133 AN: 152286 Hom.: 191 Cov.: 33 AF XY: 0.0260 AC XY: 1935 AN XY: 74472

Gnomad4 AFR AF: 0.0942

Gnomad4 AMR AF: 0.00922

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0158 Hom.: 16

Bravo AF: 0.0312

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.53
DANN	Benign	0.75
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: rs112897683; hg19: chr17-79802055;