rs3791731

Variant names:

• chr2-26190499-C-A
• rs3791731
• XM_011532567.4:c.1683+3184C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011532567.4(GAREM2):​c.1683+3184C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,648 control chromosomes in the GnomAD database, including 2,560 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 0.12 (2557 hom., cov: 32)
  • Exomes 𝑓: 0.048 (3 hom.)
• Consequence: GAREM2 XM_011532567.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

Genes affected

GAREM2 (HGNC:27172): (GRB2 associated regulator of MAPK1 subtype 2)

HADHA (HGNC:4801): (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha) This gene encodes the alpha subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids. The mitochondrial membrane-bound heterocomplex is composed of four alpha and four beta subunits, with the alpha subunit catalyzing the 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase activities. Mutations in this gene result in trifunctional protein deficiency or LCHAD deficiency. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the human genome in a head-to-head orientation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAREM2	XM_011532567.4	c.1683+3184C>A		intron_variant	Intron 6 of 6		XP_011530869.1
HADHA	NM_000182.5	c.*751G>T		downstream_gene_variant		ENST00000380649.8	NP_000173.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HADHA	ENST00000380649.8	c.*751G>T		downstream_gene_variant		1	NM_000182.5	ENSP00000370023.3
HADHA	ENST00000492433.2	c.*751G>T		downstream_gene_variant		2		ENSP00000438039.2
HADHA	ENST00000643057.1	n.*3021G>T		downstream_gene_variant				ENSP00000493761.1
HADHA	ENST00000644428.1	n.*1667G>T		downstream_gene_variant				ENSP00000495560.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18369 AN: 152046 Hom.: 2559 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.0753

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.0475 AC: 23 AN: 484 Hom.: 3 AF XY: 0.0448 AC XY: 13 AN XY: 290

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0429

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.121 AC: 18376 AN: 152164 Hom.: 2557 Cov.: 32 AF XY: 0.126 AC XY: 9403 AN XY: 74388

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.0893

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.0747

Gnomad4 FIN AF: 0.0605

Gnomad4 NFE AF: 0.0596

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0759 Hom.: 1059

Bravo AF: 0.143

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.089
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3791731; hg19: chr2-26413368;