rs4949400

Positions:

• chr1-31425285-T-C

Variant summary

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

The NM_178865.5(SERINC2):​c.393-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,414,230 control chromosomes in the GnomAD database, including 196,224 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 0.44 (16981 hom., cov: 33)
  • Exomes 𝑓: 0.52 (179243 hom.)
• Consequence: SERINC2 NM_178865.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERINC2	NM_178865.5	c.393-45T>C		intron_variant		ENST00000373709.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERINC2	ENST00000373709.8	c.393-45T>C		intron_variant		1	NM_178865.5	P1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67060 AN: 152046 Hom.: 16980 Cov.: 33

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.469

GnomAD3 exomes AF: 0.479 AC: 119645 AN: 249988 Hom.: 30840 AF XY: 0.483 AC XY: 65347 AN XY: 135214

Gnomad AFR exome AF: 0.208

Gnomad AMR exome AF: 0.466

Gnomad ASJ exome AF: 0.567

Gnomad EAS exome AF: 0.205

Gnomad SAS exome AF: 0.359

Gnomad FIN exome AF: 0.533

Gnomad NFE exome AF: 0.578

Gnomad OTH exome AF: 0.518

GnomAD4 exome AF: 0.523 AC: 659960 AN: 1262066 Hom.: 179243 Cov.: 18 AF XY: 0.520 AC XY: 331943 AN XY: 637942

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.468

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.364

Gnomad4 FIN exome AF: 0.536

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.501

GnomAD4 genome AF: 0.441 AC: 67060 AN: 152164 Hom.: 16981 Cov.: 33 AF XY: 0.437 AC XY: 32526 AN XY: 74384

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.466

Alfa AF: 0.554 Hom.: 18739

Bravo AF: 0.428

Asia WGS AF: 0.264 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.69
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4949400; hg19: chr1-31898132; COSMIC: COSV65490971;