17-81844251-CAG-C

Position:

• chr17-81844251-CAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000918.4(P4HB):​c.1447-161_1447-160del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,204 control chromosomes in the GnomAD database, including 3,155 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3155 hom., cov: 29)
• Consequence: P4HB NM_000918.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.403

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 -10 ACMG points.

• BP6: Variant 17-81844251-CAG-C is Benign according to our data. Variant chr17-81844251-CAG-C is described in ClinVar as [Benign]. Clinvar id is 1232850.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P4HB	NM_000918.4	c.1447-161_1447-160del		intron_variant		ENST00000331483.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P4HB	ENST00000331483.9	c.1447-161_1447-160del		intron_variant		1	NM_000918.4	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29919 AN: 152086 Hom.: 3155 Cov.: 29

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.197 AC: 29932 AN: 152204 Hom.: 3155 Cov.: 29 AF XY: 0.196 AC XY: 14621 AN XY: 74412

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.166

Alfa AF: 0.193 Hom.: 356

Bravo AF: 0.210

Asia WGS AF: 0.185 AC: 642 AN: 3478

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

Aug 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10567063; hg19: chr17-79802127; COSMIC: COSV58940810; COSMIC: COSV58940810;