dbSNP rs3743852: FAHD1:p.Leu153Leu (chr16-1827697-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_031208.4(FAHD1):c.459C>G(p.Leu153Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,974 control chromosomes in the GnomAD database, including 15,371 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 0.13 ( 1250 hom., cov: 33)

Exomes 𝑓: 0.14 ( 14121 hom. )

Consequence

FAHD1
NM_031208.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

11 publications found

Variant links:

Genes affected

FAHD1 (HGNC:14169): (fumarylacetoacetate hydrolase domain containing 1) Enables acetylpyruvate hydrolase activity; fumarylpyruvate hydrolase activity; and oxaloacetate decarboxylase activity. Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAHD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=1.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAHD1	NM_031208.4 link	c.459C>G	p.Leu153Leu	synonymous_variant	Exon 1 of 1	ENST00000427358.5	NP_112485.2	Q6P587

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAHD1	ENST00000427358.5 link	c.459C>G	p.Leu153Leu	synonymous_variant	Exon 1 of 1	6	NM_031208.4	ENSP00000398053.3	Q6P587
FAHD1	ENST00000382668.8 link	c.459C>G	p.Leu153Leu	synonymous_variant	Exon 1 of 2	1		ENSP00000372114.5	Q6P587
FAHD1	ENST00000382666.6 link	c.459C>G	p.Leu153Leu	synonymous_variant	Exon 1 of 3	2		ENSP00000372112.5	Q6P587

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19310

AN:

152148

Hom.:

1251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0725

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.137

GnomAD2 exomes

AF:

0.127

AC:

31916

AN:

251092

AF XY:

0.129

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.0843

Gnomad ASJ exome

AF:

0.138

Gnomad EAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.137

AC:

199901

AN:

1461708

Hom.:

14121

Cov.:

AF XY:

0.138

AC XY:

100011

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.104

AC:

3479

AN:

33478

American (AMR)

AF:

0.0874

AC:

3909

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3699

AN:

26134

East Asian (EAS)

AF:

0.146

AC:

5799

AN:

39698

South Asian (SAS)

AF:

0.138

AC:

11916

AN:

86256

European-Finnish (FIN)

AF:

0.147

AC:

7846

AN:

53334

Middle Eastern (MID)

AF:

0.147

AC:

847

AN:

5766

European-Non Finnish (NFE)

AF:

0.139

AC:

154359

AN:

1111934

Other (OTH)

AF:

0.133

AC:

8047

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

10900

21800

32700

43600

54500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5566

11132

16698

22264

27830

<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:

0.127

AC:

19315

AN:

152266

Hom.:

1250

Cov.:

AF XY:

0.127

AC XY:

9421

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.104

AC:

4311

AN:

41544

American (AMR)

AF:

0.124

AC:

1893

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

465

AN:

3472

East Asian (EAS)

AF:

0.119

AC:

614

AN:

5174

South Asian (SAS)

AF:

0.142

AC:

687

AN:

4830

European-Finnish (FIN)

AF:

0.146

AC:

1551

AN:

10604

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9416

AN:

68024

Other (OTH)

AF:

0.134

AC:

284

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

876

1753

2629

3506

4382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.134

Hom.:

465

Bravo

AF:

0.123

Asia WGS

AF:

0.0940

AC:

329

AN:

3478

EpiCase

AF:

0.133

EpiControl

AF:

0.133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.3

(source)

DANN

Benign

0.65

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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