10-50334887-T-C

Position:

• chr10-50334887-T-C

Variant summary

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

The NM_147156.4(SGMS1):​c.624-7565A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,158 control chromosomes in the GnomAD database, including 4,682 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 0.23 (4673 hom., cov: 32)
  • Exomes 𝑓: 0.29 (9 hom.)
• Consequence: SGMS1 NM_147156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGMS1	NM_147156.4	c.624-7565A>G		intron_variant		ENST00000361781.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGMS1	ENST00000361781.7	c.624-7565A>G		intron_variant		1	NM_147156.4	P1
	ENST00000624562.1	n.350T>C		non_coding_transcript_exon_variant	1/1
	ENST00000657992.1	n.269-3877T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34522 AN: 151902 Hom.: 4660 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.290 AC: 40 AN: 138 Hom.: 9 Cov.: 0 AF XY: 0.269 AC XY: 28 AN XY: 104

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.227 AC: 34565 AN: 152020 Hom.: 4673 Cov.: 32 AF XY: 0.236 AC XY: 17562 AN XY: 74310

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.243

Alfa AF: 0.187 Hom.: 1256

Bravo AF: 0.232

Asia WGS AF: 0.529 AC: 1841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
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: rs1436214; hg19: chr10-52094647;