GeneBe

5-132294369-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000471826.1(P4HA2):​n.138+809G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000722 in 554,094 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

P4HA2
ENST00000471826.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.27

Publications

10 publications found
Variant links:
Genes affected
P4HA2 (HGNC:8547): (prolyl 4-hydroxylase subunit alpha 2) 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]
SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC22A4NM_003059.3 linkc.-248C>T upstream_gene_variant ENST00000200652.4 NP_003050.2
SLC22A4XM_047417594.1 linkc.-248C>T upstream_gene_variant XP_047273550.1
SLC22A4XM_011543589.3 linkc.-248C>T upstream_gene_variant XP_011541891.1
SLC22A4XM_006714675.5 linkc.-672C>T upstream_gene_variant XP_006714738.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
P4HA2ENST00000471826.1 linkn.138+809G>A intron_variant Intron 1 of 3 1
P4HA2ENST00000431054.5 linkc.78+809G>A intron_variant Intron 1 of 5 4 ENSP00000391257.1
SLC22A4ENST00000200652.4 linkc.-248C>T upstream_gene_variant 1 NM_003059.3 ENSP00000200652.3

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151868
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000497
AC:
2
AN:
402226
Hom.:
0
AF XY:
0.00000948
AC XY:
2
AN XY:
211052
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
11182
American (AMR)
AF:
0.00
AC:
0
AN:
15028
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
12454
East Asian (EAS)
AF:
0.00
AC:
0
AN:
27150
South Asian (SAS)
AF:
0.0000492
AC:
2
AN:
40660
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
25380
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1782
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
245208
Other (OTH)
AF:
0.00
AC:
0
AN:
23382
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151868
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74168
show subpopulations
African (AFR)
AF:
0.0000242
AC:
1
AN:
41396
American (AMR)
AF:
0.00
AC:
0
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5104
South Asian (SAS)
AF:
0.000208
AC:
1
AN:
4816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10586
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67916
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
1521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.77
DANN
Benign
0.97
PhyloP100
-3.3
PromoterAI
-0.16
Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs460271; hg19: chr5-131630062; API