4-107863358-A-G

Variant names:

• chr4-107863358-A-G
• rs10516546
• NM_001375905.1:c.-245+4805A>G

Variant summary

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

The NM_001375905.1(SGMS2):​c.-245+4805A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,018 control chromosomes in the GnomAD database, including 23,445 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 0.54 (23439 hom., cov: 32)
  • Exomes 𝑓: 0.56 (6 hom.)
• Consequence: SGMS2 NM_001375905.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

Genes affected

SGMS2 (HGNC:28395): (sphingomyelin synthase 2) Sphingomyelin, a major component of cell and Golgi membranes, is made by the transfer of phosphocholine from phosphatidylcholine onto ceramide, with diacylglycerol as a side product. The protein encoded by this gene is an enzyme that catalyzes this reaction primarily at the cell membrane. The synthesis is reversible, and this enzyme can catalyze the reaction in either direction. The encoded protein is required for cell growth. Three transcript variants encoding the same protein have been found for this gene. There is evidence for more variants, but the full-length nature of their transcripts has not been determined.[provided by RefSeq, Oct 2008]

CYP2U1-AS1 (HGNC:54817): (CYP2U1 and SGMS2 antisense RNA 1)

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 (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGMS2	NM_001375905.1	c.-245+4805A>G		intron_variant	Intron 2 of 6	ENST00000690982.1	NP_001362834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGMS2	ENST00000690982.1	c.-245+4805A>G		intron_variant	Intron 2 of 6		NM_001375905.1	ENSP00000508566.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82557 AN: 151868 Hom.: 23426 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.551

GnomAD4 exome AF: 0.563 AC: 18 AN: 32 Hom.: 6 AF XY: 0.500 AC XY: 9 AN XY: 18

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.544 AC: 82607 AN: 151986 Hom.: 23439 Cov.: 32 AF XY: 0.533 AC XY: 39612 AN XY: 74294

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.545

Alfa AF: 0.531 Hom.: 43249

Bravo AF: 0.555

Asia WGS AF: 0.204 AC: 714 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	3.7
DANN	Benign	0.57

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: rs10516546; hg19: chr4-108784514;