chr4-82457719-G-A

Variant names:

• chr4-82457719-G-A
• rs1980187
• NM_021204.5:c.646+681G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021204.5(ENOPH1):​c.646+681G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 151,926 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 32)
• Consequence: ENOPH1 NM_021204.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOPH1	NM_021204.5	c.646+681G>A		intron_variant	Intron 5 of 5	ENST00000273920.8	NP_067027.1
ENOPH1	NM_001292017.2	c.382+681G>A		intron_variant	Intron 5 of 5		NP_001278946.1
ENOPH1	NR_120457.2	n.654+681G>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENOPH1	ENST00000273920.8	c.646+681G>A		intron_variant	Intron 5 of 5	1	NM_021204.5	ENSP00000273920.3
ENOPH1	ENST00000505846.5	c.208+681G>A		intron_variant	Intron 4 of 4	1		ENSP00000427209.1
ENOPH1	ENST00000509635.5	c.382+681G>A		intron_variant	Intron 5 of 5	3		ENSP00000422005.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151926 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151926 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74198

African (AFR) AF: 0.0000242 AC: 1 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 32256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.94
DANN	Benign	0.93
PhyloP100		-0.23

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: rs1980187; hg19: chr4-83378872;