4-25168420-C-G

Variant summary

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

The NR_037934.1(SEPSECS-AS1):n.82+7667C>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,126 control chromosomes in the GnomAD database, including 51,265 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 0.82 (51265 hom., cov: 31)
• Consequence: SEPSECS-AS1 NR_037934.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

Genes affected

SEPSECS-AS1 (HGNC:27737): (SEPSECS antisense RNA 1 (head to head))

PI4K2B (HGNC:18215): (phosphatidylinositol 4-kinase type 2 beta) This gene encodes a member of the type II PI4 kinase protein family. The encoded protein is primarily cytosolic and contributes to overall PI4-kinase activity along with other protein family members. This protein is involved in early T cell activation. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPSECS-AS1	NR_037934.1	n.82+7667C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPSECS-AS1	ENST00000507794.2	n.82+7667C>G		intron_variant, non_coding_transcript_variant		2
PI4K2B	ENST00000512921.4	c.-21+7667C>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124771 AN: 152008 Hom.: 51238 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.844

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.821 AC: 124849 AN: 152126 Hom.: 51265 Cov.: 31 AF XY: 0.821 AC XY: 61041 AN XY: 74350

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.851

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.829

Alfa AF: 0.827 Hom.: 6072

Bravo AF: 0.822

Asia WGS AF: 0.758 AC: 2634 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.1
Dann	Benign	0.54

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: rs2133507; hg19: chr4-25170042;