rs520046

chr6-122446048-G-Achr6-122446048-G-C

Variant summary

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

The NM_020755.4(SERINC1):c.1226+726C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,612 control chromosomes in the GnomAD database, including 37,498 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 0.70 (37498 hom., cov: 31)
• Consequence: SERINC1 NM_020755.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

Genes affected

SERINC1 (HGNC:13464): (serine incorporator 1) Predicted to enable protein-macromolecule adaptor activity. 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. Predicted to be located in endoplasmic reticulum membrane and plasma membrane. Predicted to be active in membrane. [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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SERINC1	NM_020755.4	c.1226+726C>T		intron_variant		ENST00000339697.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SERINC1	ENST00000339697.5	c.1226+726C>T		intron_variant		1	NM_020755.4	P1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106380 AN: 151492 Hom.: 37464 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.702 AC: 106469 AN: 151612 Hom.: 37498 Cov.: 31 AF XY: 0.701 AC XY: 51913 AN XY: 74094

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.699

Alfa AF: 0.613 Hom.: 1910

Bravo AF: 0.706

Asia WGS AF: 0.741 AC: 2573 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.83
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs520046; hg19: chr6-122767193;