rs4924750

chr17-18357439-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.-19-1439G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,766 control chromosomes in the GnomAD database, including 5,012 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 0.25 (5012 hom., cov: 30)
• Consequence: SHMT1 NM_004169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHMT1	NM_004169.5	c.-19-1439G>C		intron_variant		ENST00000316694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHMT1	ENST00000316694.8	c.-19-1439G>C		intron_variant		1	NM_004169.5	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37738 AN: 151648 Hom.: 5013 Cov.: 30

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.0736

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.249 AC: 37746 AN: 151766 Hom.: 5012 Cov.: 30 AF XY: 0.245 AC XY: 18138 AN XY: 74156

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.0741

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.240

Alfa AF: 0.280 Hom.: 771

Bravo AF: 0.237

Asia WGS AF: 0.127 AC: 441 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	9.6
Dann	Benign	0.90

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: rs4924750; hg19: chr17-18260753; COSMIC: COSV57398225;