rs10490964

Positions:

• chr10-50497142-C-T

Variant summary

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

The NM_147156.4(SGMS1):​c.-498+22689G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,136 control chromosomes in the GnomAD database, including 2,684 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 0.18 (2684 hom., cov: 32)
• Consequence: SGMS1 NM_147156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

Genes affected

SGMS1 (HGNC:29799): (sphingomyelin synthase 1) The protein encoded by this gene is predicted to be a five-pass transmembrane protein. This gene may be predominately expressed in brain. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGMS1	NM_147156.4	c.-498+22689G>A		intron_variant		ENST00000361781.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGMS1	ENST00000361781.7	c.-498+22689G>A		intron_variant		1	NM_147156.4	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27476 AN: 152018 Hom.: 2677 Cov.: 32

Gnomad AFR AF: 0.0951

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.176

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.181 AC: 27493 AN: 152136 Hom.: 2684 Cov.: 32 AF XY: 0.181 AC XY: 13463 AN XY: 74344

Gnomad4 AFR AF: 0.0949

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.188

Alfa AF: 0.190 Hom.: 571

Bravo AF: 0.180

Asia WGS AF: 0.216 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.5
DANN	Benign	0.71

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: rs10490964; hg19: chr10-52256902;