rs3743852

Positions:

• chr16-1827697-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FAHD1	NM_031208.4	c.459C>G	p.Leu153Leu	synonymous_variant	1/1	ENST00000427358.5	NP_112485.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAHD1	ENST00000427358.5	c.459C>G	p.Leu153Leu	synonymous_variant	1/1	6	NM_031208.4	ENSP00000398053.3
FAHD1	ENST00000382668.8	c.459C>G	p.Leu153Leu	synonymous_variant	1/2	1		ENSP00000372114.5
FAHD1	ENST00000382666.6	c.459C>G	p.Leu153Leu	synonymous_variant	1/3	2		ENSP00000372112.5

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19310 AN: 152148 Hom.: 1251 Cov.: 33

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

GnomAD3 exomes AF: 0.127 AC: 31916 AN: 251092 Hom.: 2191 AF XY: 0.129 AC XY: 17481 AN XY: 135782

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 SAS exome AF: 0.135

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.: 34 AF XY: 0.138 AC XY: 100011 AN XY: 727158

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0874

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.146

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.127 AC: 19315 AN: 152266 Hom.: 1250 Cov.: 33 AF XY: 0.127 AC XY: 9421 AN XY: 74440

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.134

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
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs3743852; hg19: chr16-1877698; COSMIC: COSV66900768; COSMIC: COSV66900768;