10-73080497-C-T

Variant names:

• chr10-73080497-C-T
• rs12570974
• NM_001017962.3:c.-32-5582G>A

Variant summary

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

The NM_001017962.3(P4HA1):​c.-32-5582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,218 control chromosomes in the GnomAD database, including 3,236 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 0.16 (3236 hom., cov: 32)
• Consequence: P4HA1 NM_001017962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P4HA1	NM_001017962.3	c.-32-5582G>A		intron_variant	Intron 1 of 14	ENST00000394890.7	NP_001017962.1
P4HA1	NM_000917.4	c.-32-5582G>A		intron_variant	Intron 1 of 14		NP_000908.2
P4HA1	NM_001142595.2	c.-125-2684G>A		intron_variant	Intron 1 of 15		NP_001136067.1
P4HA1	NM_001142596.2	c.-32-5582G>A		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.-32-5582G>A		intron_variant	Intron 1 of 14	1	NM_001017962.3	ENSP00000378353.2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24290 AN: 152100 Hom.: 3214 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0424

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.160 AC: 24358 AN: 152218 Hom.: 3236 Cov.: 32 AF XY: 0.160 AC XY: 11938 AN XY: 74434

African (AFR) AF: 0.344 AC: 14264 AN: 41480

American (AMR) AF: 0.108 AC: 1646 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 442 AN: 3468

East Asian (EAS) AF: 0.302 AC: 1565 AN: 5182

South Asian (SAS) AF: 0.233 AC: 1126 AN: 4826

European-Finnish (FIN) AF: 0.0424 AC: 450 AN: 10610

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0655 AC: 4454 AN: 68032

Other (OTH) AF: 0.129 AC: 271 AN: 2108

Alfa AF: 0.129 Hom.: 303

Bravo AF: 0.170

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.88
DANN	Benign	0.56
PhyloP100		-0.15
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: rs12570974; hg19: chr10-74840255;