rs2275435

Variant names:

• chr1-31425689-C-T
• rs2275435
• NM_178865.5:c.473-87C>T

Variant summary

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

The NM_178865.5(SERINC2):​c.473-87C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,470,186 control chromosomes in the GnomAD database, including 211,129 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 (16945 hom., cov: 33)
  • Exomes 𝑓: 0.53 (194184 hom.)
• Consequence: SERINC2 NM_178865.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 11 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=-0.83).
• 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 rank	MANE	Protein	UniProt
SERINC2	NM_178865.5	c.473-87C>T		intron_variant	Intron 4 of 9	ENST00000373709.8	NP_849196.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERINC2	ENST00000373709.8	c.473-87C>T		intron_variant	Intron 4 of 9	1	NM_178865.5	ENSP00000362813.3

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66941 AN: 151918 Hom.: 16944 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.468

GnomAD4 exome AF: 0.533 AC: 702842 AN: 1318150 Hom.: 194184 AF XY: 0.530 AC XY: 346747 AN XY: 654458

African (AFR) AF: 0.195 AC: 6028 AN: 30864

American (AMR) AF: 0.462 AC: 18626 AN: 40300

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 12455 AN: 22182

East Asian (EAS) AF: 0.183 AC: 7107 AN: 38832

South Asian (SAS) AF: 0.364 AC: 27300 AN: 74998

European-Finnish (FIN) AF: 0.538 AC: 25274 AN: 46982

Middle Eastern (MID) AF: 0.510 AC: 1912 AN: 3750

European-Non Finnish (NFE) AF: 0.573 AC: 576235 AN: 1005192

Other (OTH) AF: 0.507 AC: 27905 AN: 55050

GnomAD4 genome AF: 0.440 AC: 66942 AN: 152036 Hom.: 16945 Cov.: 33 AF XY: 0.437 AC XY: 32471 AN XY: 74330

African (AFR) AF: 0.210 AC: 8719 AN: 41454

American (AMR) AF: 0.487 AC: 7435 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1929 AN: 3464

East Asian (EAS) AF: 0.204 AC: 1052 AN: 5164

South Asian (SAS) AF: 0.347 AC: 1678 AN: 4832

European-Finnish (FIN) AF: 0.529 AC: 5601 AN: 10584

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 38994 AN: 67948

Other (OTH) AF: 0.465 AC: 980 AN: 2108

Alfa AF: 0.501 Hom.: 3118

Bravo AF: 0.427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.62
PhyloP100		-0.39
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: rs2275435; hg19: chr1-31898536; COSMIC: COSV65490231;