chr10-50504150-T-G

Position:

• chr10-50504150-T-G

Variant summary

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

The NM_147156.4(SGMS1):​c.-498+15681A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,082 control chromosomes in the GnomAD database, including 8,912 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 0.34 (8912 hom., cov: 32)
• Consequence: SGMS1 NM_147156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403

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 = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGMS1	NM_147156.4	c.-498+15681A>C		intron_variant		ENST00000361781.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGMS1	ENST00000361781.7	c.-498+15681A>C		intron_variant		1	NM_147156.4	P1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51557 AN: 151964 Hom.: 8913 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.339 AC: 51574 AN: 152082 Hom.: 8912 Cov.: 32 AF XY: 0.335 AC XY: 24939 AN XY: 74356

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.357

Alfa AF: 0.351 Hom.: 12646

Bravo AF: 0.349

Asia WGS AF: 0.232 AC: 805 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	1.3
DANN	Benign	0.69

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: rs2339507; hg19: chr10-52263910;