10-50575886-G-C

Position:

• chr10-50575886-G-C

Variant summary

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

The ENST00000361781.7(SGMS1):​c.-589+14267C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,710 control chromosomes in the GnomAD database, including 16,128 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 0.46 (16128 hom., cov: 31)
• Consequence: SGMS1 ENST00000361781.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGMS1	NM_147156.4	c.-589+14267C>G		intron_variant		ENST00000361781.7	NP_671512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGMS1	ENST00000361781.7	c.-589+14267C>G		intron_variant		1	NM_147156.4	ENSP00000354829	P1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69120 AN: 151592 Hom.: 16108 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.456 AC: 69183 AN: 151710 Hom.: 16128 Cov.: 31 AF XY: 0.456 AC XY: 33802 AN XY: 74172

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.445

Alfa AF: 0.414 Hom.: 1560

Bravo AF: 0.470

Asia WGS AF: 0.591 AC: 2054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.61
DANN	Benign	0.77

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: rs7898315; hg19: chr10-52335646;