rs2115540

Variant names:

• chr15-79897966-A-G
• rs2115540
• ENST00000479961.1:c.46-8612T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-79897966-A-G
• chr15-79897966-A-T

Variant summary

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

The ENST00000479961.1(ST20-MTHFS):​c.46-8612T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,016 control chromosomes in the GnomAD database, including 17,898 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 0.47 (17898 hom., cov: 32)
• Consequence: ST20-MTHFS ENST00000479961.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 11 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST20-MTHFS	NM_001199760.2	c.46-8612T>C		intron_variant	Intron 2 of 3		NP_001186689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST20-MTHFS	ENST00000479961.1	c.46-8612T>C		intron_variant	Intron 2 of 3	3		ENSP00000455643.1
ST20-MTHFS	ENST00000615374.5	c.46-8612T>C		intron_variant	Intron 2 of 3	3		ENSP00000489525.1
ST20-MTHFS	ENST00000494999.1	c.40-8612T>C		intron_variant	Intron 1 of 2	3		ENSP00000489298.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71973 AN: 151898 Hom.: 17882 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.474 AC: 72025 AN: 152016 Hom.: 17898 Cov.: 32 AF XY: 0.469 AC XY: 34824 AN XY: 74282

African (AFR) AF: 0.344 AC: 14265 AN: 41470

American (AMR) AF: 0.438 AC: 6685 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1674 AN: 3472

East Asian (EAS) AF: 0.325 AC: 1680 AN: 5168

South Asian (SAS) AF: 0.538 AC: 2593 AN: 4824

European-Finnish (FIN) AF: 0.494 AC: 5214 AN: 10548

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38413 AN: 67956

Other (OTH) AF: 0.464 AC: 981 AN: 2112

Alfa AF: 0.534 Hom.: 74587

Bravo AF: 0.462

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.39
PhyloP100		-0.084
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: rs2115540; hg19: chr15-80190308;