dbSNP rs2285179: GCAT:c.986+113G>A (chr22-37815947-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014291.4(GCAT):c.986+113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,247,802 control chromosomes in the GnomAD database, including 199,805 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 0.55 ( 23164 hom., cov: 32)

Exomes 𝑓: 0.56 ( 176641 hom. )

Consequence

GCAT
NM_014291.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

Publications

19 publications found

Variant links:

Genes affected

GCAT (HGNC:4188): (glycine C-acetyltransferase) The degradation of L-threonine to glycine consists of a two-step biochemical pathway involving the enzymes L-threonine dehydrogenase and 2-amino-3-ketobutyrate coenzyme A ligase. L-Threonine is first converted into 2-amino-3-ketobutyrate by L-threonine dehydrogenase. This gene encodes the second enzyme in this pathway, which then catalyzes the reaction between 2-amino-3-ketobutyrate and coenzyme A to form glycine and acetyl-CoA. The encoded enzyme is considered a class II pyridoxal-phosphate-dependent aminotransferase. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 14. [provided by RefSeq, Jan 2010]

GCAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCAT	NM_014291.4 link	c.986+113G>A		intron_variant	Intron 7 of 8	ENST00000248924.11	NP_055106.1	O75600-1A8K228

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCAT	ENST00000248924.11 link	c.986+113G>A		intron_variant	Intron 7 of 8	1	NM_014291.4	ENSP00000248924.6		O75600-1
GCAT	ENST00000323205.10 link	c.1064+113G>A		intron_variant	Intron 7 of 9	2		ENSP00000371110.3		O75600-2

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83079

AN:

151810

Hom.:

23162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.559

Gnomad ASJ

AF:

0.496

Gnomad EAS

AF:

0.862

Gnomad SAS

AF:

0.629

Gnomad FIN

AF:

0.558

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.551

Gnomad OTH

AF:

0.537

GnomAD4 exome

AF:

0.563

AC:

617071

AN:

1095874

Hom.:

176641

AF XY:

0.565

AC XY:

311108

AN XY:

550476

show subpopulations

African (AFR)

AF:

0.493

AC:

12762

AN:

25892

American (AMR)

AF:

0.572

AC:

19258

AN:

33664

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

9735

AN:

19420

East Asian (EAS)

AF:

0.825

AC:

30985

AN:

37568

South Asian (SAS)

AF:

0.632

AC:

42838

AN:

67768

European-Finnish (FIN)

AF:

0.563

AC:

25697

AN:

45648

Middle Eastern (MID)

AF:

0.556

AC:

1949

AN:

3506

European-Non Finnish (NFE)

AF:

0.548

AC:

446959

AN:

814932

Other (OTH)

AF:

0.566

AC:

26888

AN:

47476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

13783

27566

41349

55132

68915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11646

23292

34938

46584

58230

<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:

0.547

AC:

83116

AN:

151928

Hom.:

23164

Cov.:

AF XY:

0.549

AC XY:

40798

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.491

AC:

20321

AN:

41410

American (AMR)

AF:

0.559

AC:

8539

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

1720

AN:

3468

East Asian (EAS)

AF:

0.861

AC:

4456

AN:

5174

South Asian (SAS)

AF:

0.629

AC:

3028

AN:

4812

European-Finnish (FIN)

AF:

0.558

AC:

5902

AN:

10568

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.551

AC:

37411

AN:

67914

Other (OTH)

AF:

0.537

AC:

1134

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1907

3814

5722

7629

9536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.543

Hom.:

34312

Bravo

AF:

0.546

Asia WGS

AF:

0.699

AC:

2432

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.073

(source)

DANN

Benign

0.38

PhyloP100

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.99

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over