Variant 12-50104365-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005276.4(GPD1):c.42-209C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00903 in 707,786 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0079 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 37 hom. )

Consequence

GPD1
NM_005276.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.225

Variant links:

Genes affected

GPD1 (HGNC:4455): (glycerol-3-phosphate dehydrogenase 1) This gene encodes a member of the NAD-dependent glycerol-3-phosphate dehydrogenase family. The encoded protein plays a critical role in carbohydrate and lipid metabolism by catalyzing the reversible conversion of dihydroxyacetone phosphate (DHAP) and reduced nicotine adenine dinucleotide (NADH) to glycerol-3-phosphate (G3P) and NAD+. The encoded cytosolic protein and mitochondrial glycerol-3-phosphate dehydrogenase also form a glycerol phosphate shuttle that facilitates the transfer of reducing equivalents from the cytosol to mitochondria. Mutations in this gene are a cause of transient infantile hypertriglyceridemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

GPD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 12-50104365-C-A is Benign according to our data. Variant chr12-50104365-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1215556.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00791 (1205/152266) while in subpopulation NFE AF= 0.0142 (966/68004). AF 95% confidence interval is 0.0135. There are 11 homozygotes in gnomad4. There are 557 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPD1	NM_005276.4 linkuse as main transcript	c.42-209C>A		intron_variant		ENST00000301149.8	NP_005267.2
GPD1	NM_001257199.2 linkuse as main transcript	c.42-209C>A		intron_variant			NP_001244128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD1	ENST00000301149.8 linkuse as main transcript	c.42-209C>A		intron_variant		1	NM_005276.4	ENSP00000301149	P1	P21695-1

Frequencies

GnomAD3 genomes

AF:

0.00791

AC:

1204

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00672

AC:

909

AN:

135306

Hom.:

AF XY:

0.00637

AC XY:

468

AN XY:

73486

show subpopulations

Gnomad AFR exome

AF:

0.00108

Gnomad AMR exome

AF:

0.00233

Gnomad ASJ exome

AF:

0.00796

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00313

Gnomad FIN exome

AF:

0.00453

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.00757

GnomAD4 exome

AF:

0.00934

AC:

5188

AN:

555520

Hom.:

Cov.:

AF XY:

0.00906

AC XY:

2721

AN XY:

300470

show subpopulations

Gnomad4 AFR exome

AF:

0.00183

Gnomad4 AMR exome

AF:

0.00288

Gnomad4 ASJ exome

AF:

0.00825

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00319

Gnomad4 FIN exome

AF:

0.00582

Gnomad4 NFE exome

AF:

0.0132

Gnomad4 OTH exome

AF:

0.00859

GnomAD4 genome

AF:

0.00791

AC:

1205

AN:

152266

Hom.:

Cov.:

AF XY:

0.00748

AC XY:

557

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.0142

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.00715

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.0

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over