rs4924750

Variant names:

• chr17-18357439-C-G
• rs4924750
• NM_004169.5:c.-19-1439G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004169.5. 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
	SHMT1	NM_004169.5	MANE Select	c.-19-1439G>C		intron	N/A	NP_004160.3
	SHMT1	NM_148918.3		c.-19-1439G>C		intron	N/A	NP_683718.1
	SHMT1	NM_001281786.2		c.-317-1439G>C		intron	N/A	NP_001268715.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT1	ENST00000316694.8	TSL:1 MANE Select	c.-19-1439G>C		intron	N/A	ENSP00000318868.3
	SHMT1	ENST00000583780.2	TSL:1	c.-19-1439G>C		intron	N/A	ENSP00000462041.2
	SHMT1	ENST00000354098.7	TSL:1	c.-19-1439G>C		intron	N/A	ENSP00000318805.3

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

African (AFR) AF: 0.203 AC: 8379 AN: 41374

American (AMR) AF: 0.218 AC: 3305 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3472

East Asian (EAS) AF: 0.0741 AC: 384 AN: 5180

South Asian (SAS) AF: 0.169 AC: 812 AN: 4810

European-Finnish (FIN) AF: 0.289 AC: 3032 AN: 10502

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 19940 AN: 67930

Other (OTH) AF: 0.240 AC: 507 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.6
DANN	Benign	0.90
PhyloP100		-0.30
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: rs4924750; hg19: chr17-18260753; COSMIC: COSV57398225;