rs3745647

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000590627.5(GCDH):n.232T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.037 in 1,613,942 control chromosomes in the GnomAD database, including 1,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 241 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1085 hom. )

Consequence

GCDH
ENST00000590627.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0910

Publications

5 publications found

Variant links:

Genes affected

GCDH (HGNC:4189): (glutaryl-CoA dehydrogenase) The protein encoded by this gene belongs to the acyl-CoA dehydrogenase family. It catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor. The enzyme exists in the mitochondrial matrix as a homotetramer of 45-kD subunits. Mutations in this gene result in the metabolic disorder glutaric aciduria type 1, which is also known as glutaric acidemia type I. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 12. [provided by RefSeq, Mar 2013]

GCDH Gene-Disease associations (from GenCC):

glutaryl-CoA dehydrogenase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P, Myriad Women’s Health

GCDH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-12891570-T-C is Benign according to our data. Variant chr19-12891570-T-C is described in ClinVar as Benign. ClinVar VariationId is 255394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590627.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GCDH	NM_000159.4	MANE Select	c.127+48T>C	intron	N/A	NP_000150.1
GCDH	NR_102317.1		n.283T>C	non_coding_transcript_exon	Exon 3 of 11
GCDH	NM_013976.5		c.127+48T>C	intron	N/A	NP_039663.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GCDH	ENST00000590627.5	TSL:1	n.232T>C	non_coding_transcript_exon	Exon 3 of 5
GCDH	ENST00000222214.10	TSL:1 MANE Select	c.127+48T>C	intron	N/A	ENSP00000222214.4
GCDH	ENST00000591470.5	TSL:1	c.127+48T>C	intron	N/A	ENSP00000466845.1

Frequencies

GnomAD3 genomes

AF:

0.0480

AC:

7303

AN:

152178

Hom.:

243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0883

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0381

Gnomad ASJ

AF:

0.0279

Gnomad EAS

AF:

0.00770

Gnomad SAS

AF:

0.0290

Gnomad FIN

AF:

0.00903

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0381

Gnomad OTH

AF:

0.0417

GnomAD2 exomes

AF:

0.0338

AC:

8497

AN:

251134

AF XY:

0.0328

show subpopulations

Gnomad AFR exome

AF:

0.0909

Gnomad AMR exome

AF:

0.0254

Gnomad ASJ exome

AF:

0.0256

Gnomad EAS exome

AF:

0.00658

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.0377

Gnomad OTH exome

AF:

0.0372

GnomAD4 exome

AF:

0.0359

AC:

52451

AN:

1461646

Hom.:

1085

Cov.:

AF XY:

0.0357

AC XY:

25925

AN XY:

727104

show subpopulations

African (AFR)

AF:

0.0926

AC:

3100

AN:

33474

American (AMR)

AF:

0.0264

AC:

1179

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0258

AC:

674

AN:

26134

East Asian (EAS)

AF:

0.0122

AC:

483

AN:

39698

South Asian (SAS)

AF:

0.0323

AC:

2785

AN:

86242

European-Finnish (FIN)

AF:

0.0123

AC:

655

AN:

53392

Middle Eastern (MID)

AF:

0.0425

AC:

239

AN:

5618

European-Non Finnish (NFE)

AF:

0.0369

AC:

41017

AN:

1111980

Other (OTH)

AF:

0.0384

AC:

2319

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

3173

6345

9518

12690

15863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1540

3080

4620

6160

7700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0480

AC:

7307

AN:

152296

Hom.:

241

Cov.:

AF XY:

0.0452

AC XY:

3370

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0883

AC:

3668

AN:

41562

American (AMR)

AF:

0.0380

AC:

582

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0279

AC:

AN:

3472

East Asian (EAS)

AF:

0.00772

AC:

AN:

5180

South Asian (SAS)

AF:

0.0286

AC:

138

AN:

4830

European-Finnish (FIN)

AF:

0.00903

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0381

AC:

2589

AN:

68002

Other (OTH)

AF:

0.0412

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

363

726

1088

1451

1814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<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:

0.0432

Hom.:

Bravo

AF:

0.0514

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Glutaric aciduria, type 1

Benign:1

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_noAF

Benign

-0.88

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

-0.091

PromoterAI

0.045

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over