chr1-231241335-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014236.4(GNPAT):​c.-44C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,533,732 control chromosomes in the GnomAD database, including 236,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23102 hom., cov: 33)
Exomes 𝑓: 0.55 ( 213654 hom. )

Consequence

GNPAT
NM_014236.4 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.132
Variant links:
Genes affected
GNPAT (HGNC:4416): (glyceronephosphate O-acyltransferase) This gene encodes an enzyme located in the peroxisomal membrane which is essential to the synthesis of ether phospholipids. Mutations in this gene are associated with rhizomelic chondrodysplasia punctata. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 1-231241335-C-T is Benign according to our data. Variant chr1-231241335-C-T is described in ClinVar as [Benign]. Clinvar id is 296108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GNPATNM_014236.4 linkuse as main transcriptc.-44C>T 5_prime_UTR_variant 1/16 ENST00000366647.9
GNPATNM_001316350.2 linkuse as main transcriptc.-44C>T 5_prime_UTR_variant 1/15
GNPATXM_005273313.5 linkuse as main transcriptc.-44C>T 5_prime_UTR_variant 1/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GNPATENST00000366647.9 linkuse as main transcriptc.-44C>T 5_prime_UTR_variant 1/161 NM_014236.4 P1O15228-1
GNPATENST00000416000.1 linkuse as main transcriptc.-44C>T 5_prime_UTR_variant 1/135
GNPATENST00000436239.5 linkuse as main transcriptc.-44C>T 5_prime_UTR_variant 1/63
GNPATENST00000644483.1 linkuse as main transcriptc.-44C>T 5_prime_UTR_variant, NMD_transcript_variant 1/17

Frequencies

GnomAD3 genomes
AF:
0.549
AC:
83376
AN:
151936
Hom.:
23065
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.569
Gnomad AMI
AF:
0.428
Gnomad AMR
AF:
0.592
Gnomad ASJ
AF:
0.614
Gnomad EAS
AF:
0.616
Gnomad SAS
AF:
0.624
Gnomad FIN
AF:
0.425
Gnomad MID
AF:
0.487
Gnomad NFE
AF:
0.534
Gnomad OTH
AF:
0.570
GnomAD3 exomes
AF:
0.554
AC:
138395
AN:
249700
Hom.:
38910
AF XY:
0.556
AC XY:
75079
AN XY:
135086
show subpopulations
Gnomad AFR exome
AF:
0.570
Gnomad AMR exome
AF:
0.607
Gnomad ASJ exome
AF:
0.595
Gnomad EAS exome
AF:
0.594
Gnomad SAS exome
AF:
0.624
Gnomad FIN exome
AF:
0.434
Gnomad NFE exome
AF:
0.529
Gnomad OTH exome
AF:
0.563
GnomAD4 exome
AF:
0.553
AC:
764355
AN:
1381678
Hom.:
213654
Cov.:
22
AF XY:
0.555
AC XY:
384322
AN XY:
692114
show subpopulations
Gnomad4 AFR exome
AF:
0.566
Gnomad4 AMR exome
AF:
0.604
Gnomad4 ASJ exome
AF:
0.598
Gnomad4 EAS exome
AF:
0.602
Gnomad4 SAS exome
AF:
0.620
Gnomad4 FIN exome
AF:
0.434
Gnomad4 NFE exome
AF:
0.548
Gnomad4 OTH exome
AF:
0.563
GnomAD4 genome
AF:
0.549
AC:
83456
AN:
152054
Hom.:
23102
Cov.:
33
AF XY:
0.544
AC XY:
40466
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.569
Gnomad4 AMR
AF:
0.593
Gnomad4 ASJ
AF:
0.614
Gnomad4 EAS
AF:
0.617
Gnomad4 SAS
AF:
0.624
Gnomad4 FIN
AF:
0.425
Gnomad4 NFE
AF:
0.534
Gnomad4 OTH
AF:
0.571
Alfa
AF:
0.548
Hom.:
37357
Bravo
AF:
0.561
Asia WGS
AF:
0.605
AC:
2106
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Rhizomelic chondrodysplasia punctata type 2 Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 10, 2021- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2016This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
9.7
DANN
Benign
0.70

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs518686; hg19: chr1-231377081; COSMIC: COSV59641814; COSMIC: COSV59641814; API