1-31411078-T-C

Variant names:

• chr1-31411078-T-C
• rs4478858
• NM_001199038.2:c.66+643T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 38 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=-0.98).
• 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 rank	MANE	Protein	UniProt
SERINC2	NM_001199038.2	c.66+643T>C		intron_variant	Intron 2 of 10		NP_001185967.1
SERINC2	NM_001199037.2	c.51+643T>C		intron_variant	Intron 1 of 9		NP_001185966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERINC2	ENST00000373710.5	c.66+643T>C		intron_variant	Intron 2 of 10	2		ENSP00000362814.1
SERINC2	ENST00000536859.5	c.51+643T>C		intron_variant	Intron 1 of 9	2		ENSP00000444307.1
SERINC2	ENST00000487207.5	n.219+643T>C		intron_variant	Intron 1 of 4	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

African (AFR) AF: 0.536 AC: 22189 AN: 41414

American (AMR) AF: 0.479 AC: 7312 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1502 AN: 3472

East Asian (EAS) AF: 0.799 AC: 4141 AN: 5180

South Asian (SAS) AF: 0.653 AC: 3148 AN: 4820

European-Finnish (FIN) AF: 0.470 AC: 4964 AN: 10566

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.425 AC: 28865 AN: 67968

Other (OTH) AF: 0.484 AC: 1022 AN: 2112

Alfa AF: 0.447 Hom.: 45992

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
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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