chr10-50394027-T-C

Position:

• chr10-50394027-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.-232+39449A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,106 control chromosomes in the GnomAD database, including 46,843 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 0.78 (46843 hom., cov: 32)
• Consequence: SGMS1 NM_147156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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]

SGMS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGMS1	NM_147156.4	c.-232+39449A>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.-232+39449A>G		intron_variant		1	NM_147156.4	ENSP00000354829.2

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118872 AN: 151988 Hom.: 46779 Cov.: 32

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.782 AC: 118995 AN: 152106 Hom.: 46843 Cov.: 32 AF XY: 0.785 AC XY: 58353 AN XY: 74342

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.840

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.809

Alfa AF: 0.754 Hom.: 5077

Bravo AF: 0.791

Asia WGS AF: 0.911 AC: 3166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.30
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2339402; hg19: chr10-52153787;