rs2339507

Variant names:

• chr10-50504150-T-G
• rs2339507
• NM_147156.4:c.-498+15681A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SGMS1	NM_147156.4	c.-498+15681A>C		intron_variant	Intron 3 of 10	ENST00000361781.7	NP_671512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGMS1	ENST00000361781.7	c.-498+15681A>C		intron_variant	Intron 3 of 10	1	NM_147156.4	ENSP00000354829.2

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

African (AFR) AF: 0.336 AC: 13952 AN: 41468

American (AMR) AF: 0.408 AC: 6231 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1412 AN: 3464

East Asian (EAS) AF: 0.268 AC: 1384 AN: 5164

South Asian (SAS) AF: 0.249 AC: 1201 AN: 4824

European-Finnish (FIN) AF: 0.287 AC: 3036 AN: 10572

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23154 AN: 68002

Other (OTH) AF: 0.357 AC: 754 AN: 2110

Alfa AF: 0.350 Hom.: 15928

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
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2339507; hg19: chr10-52263910;