Genetic Variant SGMS2:c.-245+4805A>G (chr4-107863358-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.165

Publications

1 publications found

Variant links:

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]

SGMS2 links:

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

CYP2U1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	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 link	c.-245+4805A>G		intron_variant	Intron 2 of 6		NM_001375905.1	ENSP00000508566.1		Q8NHU3

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

82557

AN:

151868

Hom.:

23426

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.567

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.544

AC:

82607

AN:

151986

Hom.:

23439

Cov.:

AF XY:

0.533

AC XY:

39612

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.669

AC:

27736

AN:

41470

American (AMR)

AF:

0.504

AC:

7686

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.550

AC:

1907

AN:

3470

East Asian (EAS)

AF:

0.162

AC:

834

AN:

5150

South Asian (SAS)

AF:

0.279

AC:

1341

AN:

4808

European-Finnish (FIN)

AF:

0.486

AC:

5134

AN:

10556

Middle Eastern (MID)

AF:

0.521

AC:

152

AN:

292

European-Non Finnish (NFE)

AF:

0.534

AC:

36263

AN:

67956

Other (OTH)

AF:

0.545

AC:

1151

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1866

3732

5599

7465

9331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

686

1372

2058

2744

3430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.534

Hom.:

92982

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

(source)

DANN

Benign

0.57

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over