NM_147156.4:c.624-7565A>G

Variant names:

• chr10-50334887-T-C
• rs1436214
• NM_147156.4:c.624-7565A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_147156.4(SGMS1):​c.624-7565A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,158 control chromosomes in the GnomAD database, including 4,682 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 0.23 (4673 hom., cov: 32)
  • Exomes 𝑓: 0.29 (9 hom.)
• Consequence: SGMS1 NM_147156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 2 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]

ENSG00000279863 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGMS1	NM_147156.4	c.624-7565A>G		intron_variant	Intron 7 of 10	ENST00000361781.7	NP_671512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGMS1	ENST00000361781.7	c.624-7565A>G		intron_variant	Intron 7 of 10	1	NM_147156.4	ENSP00000354829.2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34522 AN: 151902 Hom.: 4660 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.290 AC: 40 AN: 138 Hom.: 9 Cov.: 0 AF XY: 0.269 AC XY: 28 AN XY: 104

African (AFR) AF: 0.500 AC: 5 AN: 10

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.750 AC: 6 AN: 8

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.204 AC: 22 AN: 108

Other (OTH) AF: 1.00 AC: 6 AN: 6

GnomAD4 genome AF: 0.227 AC: 34565 AN: 152020 Hom.: 4673 Cov.: 32 AF XY: 0.236 AC XY: 17562 AN XY: 74310

African (AFR) AF: 0.213 AC: 8832 AN: 41466

American (AMR) AF: 0.284 AC: 4340 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3468

East Asian (EAS) AF: 0.633 AC: 3268 AN: 5166

South Asian (SAS) AF: 0.493 AC: 2365 AN: 4800

European-Finnish (FIN) AF: 0.183 AC: 1933 AN: 10578

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.185 AC: 12549 AN: 67946

Other (OTH) AF: 0.243 AC: 513 AN: 2108

Alfa AF: 0.197 Hom.: 2054

Bravo AF: 0.232

Asia WGS AF: 0.529 AC: 1841 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	0.13
DANN	Benign	0.63
PhyloP100		-1.4
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: rs1436214; hg19: chr10-52094647;