rs6480668

Positions:

• chr10-73089568-A-G
• chr10-73089568-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017962.3(P4HA1):​c.-33+7198T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,028 control chromosomes in the GnomAD database, including 3,139 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 (3139 hom., cov: 31)
• Consequence: P4HA1 NM_001017962.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P4HA1	NM_001017962.3	c.-33+7198T>C		intron_variant		ENST00000394890.7
P4HA1	NM_000917.4	c.-33+7198T>C		intron_variant
P4HA1	NM_001142595.2	c.-126+7198T>C		intron_variant
P4HA1	NM_001142596.2	c.-33+7198T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P4HA1	ENST00000394890.7	c.-33+7198T>C		intron_variant		1	NM_001017962.3	A1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23994 AN: 151910 Hom.: 3117 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.158 AC: 24062 AN: 152028 Hom.: 3139 Cov.: 31 AF XY: 0.159 AC XY: 11784 AN XY: 74320

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.0419

Gnomad4 NFE AF: 0.0654

Gnomad4 OTH AF: 0.127

Alfa AF: 0.121 Hom.: 322

Bravo AF: 0.169

Asia WGS AF: 0.261 AC: 906 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.3
DANN	Benign	0.66

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: rs6480668; hg19: chr10-74849326;