rs12573512

Variant names:

• chr10-73081217-A-G
• rs12573512
• NM_001017962.3:c.-32-6302T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017962.3(P4HA1):​c.-32-6302T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,054 control chromosomes in the GnomAD database, including 1,265 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 0.11 (1265 hom., cov: 32)
• Consequence: P4HA1 NM_001017962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.860
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P4HA1	NM_001017962.3	c.-32-6302T>C		intron_variant	Intron 1 of 14	ENST00000394890.7	NP_001017962.1
P4HA1	NM_000917.4	c.-32-6302T>C		intron_variant	Intron 1 of 14		NP_000908.2
P4HA1	NM_001142595.2	c.-125-3404T>C		intron_variant	Intron 1 of 15		NP_001136067.1
P4HA1	NM_001142596.2	c.-32-6302T>C		intron_variant	Intron 1 of 13		NP_001136068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P4HA1	ENST00000394890.7	c.-32-6302T>C		intron_variant	Intron 1 of 14	1	NM_001017962.3	ENSP00000378353.2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16281 AN: 151936 Hom.: 1246 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.0411

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0610

Gnomad OTH AF: 0.0957

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

GnomAD4 genome AF: 0.107 AC: 16333 AN: 152054 Hom.: 1265 Cov.: 32 AF XY: 0.109 AC XY: 8137 AN XY: 74324

African (AFR) AF: 0.169 AC: 7003 AN: 41382

American (AMR) AF: 0.0891 AC: 1361 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 388 AN: 3464

East Asian (EAS) AF: 0.301 AC: 1559 AN: 5180

South Asian (SAS) AF: 0.231 AC: 1109 AN: 4804

European-Finnish (FIN) AF: 0.0411 AC: 436 AN: 10604

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0610 AC: 4150 AN: 68026

Other (OTH) AF: 0.0961 AC: 203 AN: 2112

Alfa AF: 0.0812 Hom.: 300

Bravo AF: 0.111

Asia WGS AF: 0.248 AC: 860 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.8
DANN	Benign	0.67
PhyloP100		0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs12573512; hg19: chr10-74840975;