10-50359537-T-C

Variant names:

• chr10-50359537-T-C
• rs2574975
• NM_147156.4:c.-231-15192A>G

Variant summary

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

The NM_147156.4(SGMS1):​c.-231-15192A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,970 control chromosomes in the GnomAD database, including 7,887 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 0.32 (7887 hom., cov: 32)
• Consequence: SGMS1 NM_147156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGMS1	NM_147156.4	c.-231-15192A>G		intron_variant	Intron 6 of 10	ENST00000361781.7	NP_671512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGMS1	ENST00000361781.7	c.-231-15192A>G		intron_variant	Intron 6 of 10	1	NM_147156.4	ENSP00000354829.2

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48181 AN: 151850 Hom.: 7879 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.317 AC: 48224 AN: 151970 Hom.: 7887 Cov.: 32 AF XY: 0.316 AC XY: 23469 AN XY: 74256

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.340

Alfa AF: 0.338 Hom.: 1146

Bravo AF: 0.317

Asia WGS AF: 0.325 AC: 1132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.63

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: rs2574975; hg19: chr10-52119297;