chr4-82448134-A-G

Variant names:

• chr4-82448134-A-G
• rs4285076
• NM_021204.5:c.186+113A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ENOPH1	NM_021204.5	c.186+113A>G		intron_variant	Intron 2 of 5	ENST00000273920.8	NP_067027.1
ENOPH1	NM_001292017.2	c.-79+113A>G		intron_variant	Intron 2 of 5		NP_001278946.1
ENOPH1	NR_120457.2	n.397+113A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENOPH1	ENST00000273920.8	c.186+113A>G		intron_variant	Intron 2 of 5	1	NM_021204.5	ENSP00000273920.3
ENOPH1	ENST00000505846.5	c.-50+113A>G		intron_variant	Intron 2 of 4	1		ENSP00000427209.1
ENOPH1	ENST00000509635.5	c.-79+113A>G		intron_variant	Intron 2 of 5	3		ENSP00000422005.1

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

African (AFR) AF: 0.933 AC: 11206 AN: 12006

American (AMR) AF: 0.780 AC: 12752 AN: 16342

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 10815 AN: 13472

East Asian (EAS) AF: 0.320 AC: 9163 AN: 28596

South Asian (SAS) AF: 0.786 AC: 28245 AN: 35942

European-Finnish (FIN) AF: 0.727 AC: 30338 AN: 41730

Middle Eastern (MID) AF: 0.825 AC: 2888 AN: 3500

European-Non Finnish (NFE) AF: 0.705 AC: 200608 AN: 284686

Other (OTH) AF: 0.725 AC: 18478 AN: 25486

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

African (AFR) AF: 0.930 AC: 38660 AN: 41564

American (AMR) AF: 0.796 AC: 12170 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2756 AN: 3468

East Asian (EAS) AF: 0.379 AC: 1960 AN: 5168

South Asian (SAS) AF: 0.787 AC: 3796 AN: 4826

European-Finnish (FIN) AF: 0.746 AC: 7873 AN: 10560

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48140 AN: 67986

Other (OTH) AF: 0.779 AC: 1643 AN: 2108

Alfa AF: 0.729 Hom.: 133146

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
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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