rs4949402

chr1-31425387-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_178865.5(SERINC2):c.450T>C(p.Ile150=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,609,294 control chromosomes in the GnomAD database, including 234,734 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 0.45 (17229 hom., cov: 33)
  • Exomes 𝑓: 0.54 (217505 hom.)
• Consequence: SERINC2 NM_178865.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

Genes affected

SERINC2 (HGNC:23231): (serine incorporator 2) Predicted to be involved in several processes, including phosphatidylserine metabolic process; positive regulation of CDP-diacylglycerol-serine O-phosphatidyltransferase activity; and positive regulation of serine C-palmitoyltransferase activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.326 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERINC2	NM_178865.5	c.450T>C	p.Ile150=	synonymous_variant	4/10	ENST00000373709.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERINC2	ENST00000373709.8	c.450T>C	p.Ile150=	synonymous_variant	4/10	1	NM_178865.5	P1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67896 AN: 151854 Hom.: 17228 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.473

GnomAD3 exomes AF: 0.491 AC: 123376 AN: 251328 Hom.: 31912 AF XY: 0.495 AC XY: 67237 AN XY: 135866

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.467

Gnomad ASJ exome AF: 0.567

Gnomad EAS exome AF: 0.349

Gnomad SAS exome AF: 0.366

Gnomad FIN exome AF: 0.534

Gnomad NFE exome AF: 0.579

Gnomad OTH exome AF: 0.524

GnomAD4 exome AF: 0.539 AC: 785556 AN: 1457322 Hom.: 217505 Cov.: 34 AF XY: 0.536 AC XY: 388456 AN XY: 725276

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.310

Gnomad4 SAS exome AF: 0.373

Gnomad4 FIN exome AF: 0.536

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.516

GnomAD4 genome AF: 0.447 AC: 67895 AN: 151972 Hom.: 17229 Cov.: 33 AF XY: 0.444 AC XY: 32985 AN XY: 74282

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.470

Alfa AF: 0.542 Hom.: 24353

Bravo AF: 0.434

Asia WGS AF: 0.319 AC: 1112 AN: 3478

EpiCase AF: 0.582

EpiControl AF: 0.581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	10
Dann	Benign	0.79

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: rs4949402; hg19: chr1-31898234; COSMIC: COSV65489366;