rs7556371

Variant names:

• chr1-204488208-G-A
• rs7556371
• NM_001377334.1:c.-85+6148C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-204488208-G-A
• chr1-204488208-G-C
• chr1-204488208-G-T

Variant summary

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

The NM_001377334.1(PIK3C2B):​c.-85+6148C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,128 control chromosomes in the GnomAD database, including 31,615 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 0.63 (31615 hom., cov: 32)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 26 publications found

Genes affected

PIK3C2B (HGNC:8972): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta) The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is sensitive to low nanomolar levels of the inhibitor wortmanin. The C2 domain of this protein was shown to bind phospholipids but not Ca2+, which suggests that this enzyme may function in a calcium-independent manner. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2B	NM_001377334.1	c.-85+6148C>T		intron_variant	Intron 1 of 32	ENST00000684373.1	NP_001364263.1
PIK3C2B	NM_002646.4	c.-85+1608C>T		intron_variant	Intron 3 of 34		NP_002637.3
PIK3C2B	NM_001377335.1	c.-85+1608C>T		intron_variant	Intron 3 of 35		NP_001364264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2B	ENST00000684373.1	c.-85+6148C>T		intron_variant	Intron 1 of 32		NM_001377334.1	ENSP00000507222.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95547 AN: 152008 Hom.: 31610 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.683

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.628 AC: 95569 AN: 152128 Hom.: 31615 Cov.: 32 AF XY: 0.634 AC XY: 47172 AN XY: 74364

African (AFR) AF: 0.405 AC: 16794 AN: 41458

American (AMR) AF: 0.634 AC: 9704 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2234 AN: 3468

East Asian (EAS) AF: 0.705 AC: 3648 AN: 5176

South Asian (SAS) AF: 0.664 AC: 3198 AN: 4816

European-Finnish (FIN) AF: 0.834 AC: 8825 AN: 10582

Middle Eastern (MID) AF: 0.678 AC: 198 AN: 292

European-Non Finnish (NFE) AF: 0.720 AC: 48937 AN: 68012

Other (OTH) AF: 0.622 AC: 1315 AN: 2114

Alfa AF: 0.681 Hom.: 107332

Bravo AF: 0.603

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.74
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7556371; hg19: chr1-204457336;