ENST00000479961.1:c.45+6996G>A

Variant names:

• chr15-79900633-C-T
• rs36035742
• ENST00000479961.1:c.45+6996G>A

Variant summary

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

The ENST00000479961.1(ST20-MTHFS):​c.45+6996G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 152,090 control chromosomes in the GnomAD database, including 494 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 0.050 (494 hom., cov: 33)
• Consequence: ST20-MTHFS ENST00000479961.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664
• Publications: 3 publications found

Genes affected

ST20-MTHFS (HGNC:44655): (ST20-MTHFS readthrough) This locus represents naturally occurring read-through transcription between the neighboring suppressor of tumorigenicity 20 and 5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase) genes on chromosome 15. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]

ST20 (HGNC:33520): (suppressor of tumorigenicity 20) Enables cysteine-type endopeptidase activator activity involved in apoptotic process. Involved in several processes, including apoptotic signaling pathway; cellular response to UV-C; and positive regulation of nitrogen compound metabolic process. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000479961.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST20-MTHFS	NM_001199760.2		c.45+6996G>A		intron	N/A	NP_001186689.1
	ST20	NR_037652.2		n.358-1508G>A		intron	N/A
	ST20	NR_037653.2		n.380-1508G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST20-MTHFS	ENST00000479961.1	TSL:3	c.45+6996G>A		intron	N/A	ENSP00000455643.1
	ST20	ENST00000478497.5	TSL:1	n.726-1508G>A		intron	N/A
	ST20	ENST00000485386.1	TSL:1	n.308-1508G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 7536 AN: 151972 Hom.: 494 Cov.: 33

Gnomad AFR AF: 0.00892

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0412

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

GnomAD4 genome AF: 0.0495 AC: 7533 AN: 152090 Hom.: 494 Cov.: 33 AF XY: 0.0554 AC XY: 4117 AN XY: 74322

African (AFR) AF: 0.00889 AC: 369 AN: 41496

American (AMR) AF: 0.0173 AC: 264 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3468

East Asian (EAS) AF: 0.314 AC: 1621 AN: 5158

South Asian (SAS) AF: 0.120 AC: 577 AN: 4814

European-Finnish (FIN) AF: 0.127 AC: 1340 AN: 10574

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0462 AC: 3138 AN: 67978

Other (OTH) AF: 0.0408 AC: 86 AN: 2110

Alfa AF: 0.0540 Hom.: 571

Bravo AF: 0.0381

Asia WGS AF: 0.190 AC: 655 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.65
PhyloP100		0.66
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: rs36035742; hg19: chr15-80192975;