chr1-31411078-T-C

Position:

• chr1-31411078-T-C

Variant summary

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

The NM_001199038.2(SERINC2):​c.66+643T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,008 control chromosomes in the GnomAD database, including 18,597 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 0.49 (18597 hom., cov: 31)
• Consequence: SERINC2 NM_001199038.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERINC2	NM_001199037.2	c.51+643T>C		intron_variant			NP_001185966.1
SERINC2	NM_001199038.2	c.66+643T>C		intron_variant			NP_001185967.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERINC2	ENST00000373710.5	c.66+643T>C		intron_variant		2		ENSP00000362814
SERINC2	ENST00000536859.5	c.51+643T>C		intron_variant		2		ENSP00000444307
SERINC2	ENST00000487207.5	n.219+643T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73690 AN: 151892 Hom.: 18552 Cov.: 31

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.480

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.485 AC: 73790 AN: 152008 Hom.: 18597 Cov.: 31 AF XY: 0.492 AC XY: 36571 AN XY: 74318

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.484

Alfa AF: 0.436 Hom.: 16148

Bravo AF: 0.487

Asia WGS AF: 0.717 AC: 2492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.3
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4478858; hg19: chr1-31883925; COSMIC: COSV65489776; COSMIC: COSV65489776;