4-82457719-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021204.5(ENOPH1):​c.646+681G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,956 control chromosomes in the GnomAD database, including 22,052 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 0.54 (22052 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENOPH1	NM_021204.5	c.646+681G>T		intron_variant	Intron 5 of 5	ENST00000273920.8	NP_067027.1
ENOPH1	NM_001292017.2	c.382+681G>T		intron_variant	Intron 5 of 5		NP_001278946.1
ENOPH1	NR_120457.2	n.654+681G>T		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>T		intron_variant	Intron 5 of 5	1	NM_021204.5	ENSP00000273920.3
ENOPH1	ENST00000505846.5	c.208+681G>T		intron_variant	Intron 4 of 4	1		ENSP00000427209.1
ENOPH1	ENST00000509635.5	c.382+681G>T		intron_variant	Intron 5 of 5	3		ENSP00000422005.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81523 AN: 151840 Hom.: 22030 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.537 AC: 81590 AN: 151956 Hom.: 22052 Cov.: 32 AF XY: 0.544 AC XY: 40375 AN XY: 74262

African (AFR) AF: 0.513 AC: 21260 AN: 41426

American (AMR) AF: 0.582 AC: 8896 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1696 AN: 3472

East Asian (EAS) AF: 0.515 AC: 2658 AN: 5158

South Asian (SAS) AF: 0.650 AC: 3133 AN: 4820

European-Finnish (FIN) AF: 0.603 AC: 6368 AN: 10558

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35758 AN: 67930

Other (OTH) AF: 0.525 AC: 1106 AN: 2108

Alfa AF: 0.523 Hom.: 32256

Bravo AF: 0.530

Asia WGS AF: 0.570 AC: 1981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.74
DANN	Benign	0.57
PhyloP100		-0.23
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: rs1980187; hg19: chr4-83378872;