rs1130886

Variant names:

• chr10-73043919-T-C
• rs1130886
• ENST00000263556.3:c.1116A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BP6

The NM_001017962.3(P4HA1):​c.1148+1062A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,613,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: P4HA1 NM_001017962.3 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.05
• Publications: 2 publications found

Genes affected

P4HA1 (HGNC:8546): (prolyl 4-hydroxylase subunit alpha 1) This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 10-73043919-T-C is Benign according to our data. Variant chr10-73043919-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3041061.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P4HA1	NM_001017962.3	c.1148+1062A>G		intron_variant	Intron 9 of 14	ENST00000394890.7	NP_001017962.1
P4HA1	NM_000917.4	c.1116A>G	p.Lys372Lys	synonymous_variant	Exon 9 of 15		NP_000908.2
P4HA1	NM_001142596.2	c.1116A>G	p.Lys372Lys	synonymous_variant	Exon 9 of 14		NP_001136068.1
P4HA1	NM_001142595.2	c.1148+1062A>G		intron_variant	Intron 10 of 15		NP_001136067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P4HA1	ENST00000394890.7	c.1148+1062A>G		intron_variant	Intron 9 of 14	1	NM_001017962.3	ENSP00000378353.2

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000287 AC: 72 AN: 251062 AF XY: 0.000273

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000697

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000405

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000302 AC: 441 AN: 1460756 Hom.: 0 Cov.: 29 AF XY: 0.000305 AC XY: 222 AN XY: 726730

African (AFR) AF: 0.0000299 AC: 1 AN: 33440

American (AMR) AF: 0.000761 AC: 34 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86134

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53410

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000341 AC: 379 AN: 1111186

Other (OTH) AF: 0.000331 AC: 20 AN: 60364

GnomAD4 genome AF: 0.000236 AC: 36 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74464

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.000458 AC: 7 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68014

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000503 Hom.: 0

Bravo AF: 0.000340

EpiCase AF: 0.000602

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

P4HA1-related disorder Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.62
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1130886; hg19: chr10-74803677;