rs4285076

chr4-82448134-A-G

Variant summary

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

The NM_021204.5(ENOPH1):c.186+113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 613,924 control chromosomes in the GnomAD database, including 164,011 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 0.78 (46839 hom., cov: 32)
  • Exomes 𝑓: 0.70 (117172 hom.)
• Consequence: ENOPH1 NM_021204.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

Genes affected

ENOPH1 (HGNC:24599): (enolase-phosphatase 1) Enables acireductone synthase activity. Involved in L-methionine salvage from methylthioadenosine. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENOPH1	NM_021204.5	c.186+113A>G		intron_variant		ENST00000273920.8
ENOPH1	NM_001292017.2	c.-79+113A>G		intron_variant
ENOPH1	NR_120457.2	n.397+113A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENOPH1	ENST00000273920.8	c.186+113A>G		intron_variant		1	NM_021204.5	P1
ENOPH1	ENST00000505846.5	c.-50+113A>G		intron_variant		1
ENOPH1	ENST00000509635.5	c.-79+113A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117898 AN: 152046 Hom.: 46782 Cov.: 32

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.703 AC: 324493 AN: 461760 Hom.: 117172 AF XY: 0.707 AC XY: 172078 AN XY: 243328

Gnomad4 AFR exome AF: 0.933

Gnomad4 AMR exome AF: 0.780

Gnomad4 ASJ exome AF: 0.803

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.786

Gnomad4 FIN exome AF: 0.727

Gnomad4 NFE exome AF: 0.705

Gnomad4 OTH exome AF: 0.725

GnomAD4 genome AF: 0.776 AC: 118016 AN: 152164 Hom.: 46839 Cov.: 32 AF XY: 0.777 AC XY: 57770 AN XY: 74388

Gnomad4 AFR AF: 0.930

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.779

Alfa AF: 0.726 Hom.: 55965

Bravo AF: 0.780

Asia WGS AF: 0.628 AC: 2183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.20
Dann	Benign	0.56

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: rs4285076; hg19: chr4-83369287; COSMIC: COSV56731151; COSMIC: COSV56731151;