rs4949400

Variant names:

• chr1-31425285-T-C
• rs4949400
• NM_178865.5:c.393-45T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178865.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERINC2	NM_178865.5	MANE Select	c.393-45T>C		intron	N/A	NP_849196.2
	SERINC2	NM_001199038.2		c.420-45T>C		intron	N/A	NP_001185967.1
	SERINC2	NM_001199037.2		c.405-45T>C		intron	N/A	NP_001185966.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERINC2	ENST00000373709.8	TSL:1 MANE Select	c.393-45T>C		intron	N/A	ENSP00000362813.3
	SERINC2	ENST00000373710.5	TSL:2	c.420-45T>C		intron	N/A	ENSP00000362814.1
	SERINC2	ENST00000536384.2	TSL:2	c.405-45T>C		intron	N/A	ENSP00000439048.1

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

GnomAD2 exomes AF: 0.479 AC: 119645 AN: 249988 AF XY: 0.483

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 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

African (AFR) AF: 0.193 AC: 5825 AN: 30108

American (AMR) AF: 0.468 AC: 20802 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 13942 AN: 24902

East Asian (EAS) AF: 0.182 AC: 7087 AN: 38886

South Asian (SAS) AF: 0.364 AC: 30067 AN: 82608

European-Finnish (FIN) AF: 0.536 AC: 28572 AN: 53306

Middle Eastern (MID) AF: 0.515 AC: 2767 AN: 5374

European-Non Finnish (NFE) AF: 0.564 AC: 523899 AN: 928540

Other (OTH) AF: 0.501 AC: 26999 AN: 53888

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

African (AFR) AF: 0.211 AC: 8779 AN: 41540

American (AMR) AF: 0.488 AC: 7460 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1933 AN: 3466

East Asian (EAS) AF: 0.204 AC: 1057 AN: 5186

South Asian (SAS) AF: 0.347 AC: 1674 AN: 4822

European-Finnish (FIN) AF: 0.529 AC: 5586 AN: 10566

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 39032 AN: 67970

Other (OTH) AF: 0.466 AC: 985 AN: 2114

Alfa AF: 0.536 Hom.: 24485

Bravo AF: 0.428

Asia WGS AF: 0.264 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.69
DANN	Benign	0.71
PhyloP100		-0.034
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4949400; hg19: chr1-31898132; COSMIC: COSV65490971;