rs2168781

chr17-18337432-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004169.5(SHMT1):c.815-1757G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,994 control chromosomes in the GnomAD database, including 19,926 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 0.49 (19926 hom., cov: 31)
• Consequence: SHMT1 NM_004169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

Genes affected

SHMT1 (HGNC:10850): (serine hydroxymethyltransferase 1) This gene encodes the cytosolic form of serine hydroxymethyltransferase, a pyridoxal phosphate-containing enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. This reaction provides one-carbon units for synthesis of methionine, thymidylate, and purines in the cytoplasm. This gene is located within the Smith-Magenis syndrome region on chromosome 17. A pseudogene of this gene is located on the short arm of chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHMT1	NM_004169.5	c.815-1757G>C		intron_variant		ENST00000316694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHMT1	ENST00000316694.8	c.815-1757G>C		intron_variant		1	NM_004169.5	P1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75064 AN: 151876 Hom.: 19893 Cov.: 31

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.494 AC: 75152 AN: 151994 Hom.: 19926 Cov.: 31 AF XY: 0.491 AC XY: 36501 AN XY: 74286

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.481

Alfa AF: 0.488 Hom.: 2341

Bravo AF: 0.498

Asia WGS AF: 0.340 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.88
Dann	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs2168781; hg19: chr17-18240746; COSMIC: COSV57398176; COSMIC: COSV57398176;