Variant rs2306364 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006747.4(SIPA1):c.1026G>A(p.Ala342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,613,408 control chromosomes in the GnomAD database, including 139,988 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 0.39 ( 12293 hom., cov: 32)

Exomes 𝑓: 0.41 ( 127695 hom. )

Consequence

SIPA1
NM_006747.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -7.71

Variant links:

Genes affected

SIPA1 (HGNC:10885): (signal-induced proliferation-associated 1) The product of this gene is a mitogen induced GTPase activating protein (GAP). It exhibits a specific GAP activity for Ras-related regulatory proteins Rap1 and Rap2, but not for Ran or other small GTPases. This protein may also hamper mitogen-induced cell cycle progression when abnormally or prematurely expressed. It is localized to the perinuclear region. Two alternatively spliced variants encoding the same isoform have been characterized to date. [provided by RefSeq, Jul 2008]

SIPA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP7

Synonymous conserved (PhyloP=-7.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIPA1	NM_006747.4 linkuse as main transcript	c.1026G>A	p.Ala342=	synonymous_variant	5/16	ENST00000534313.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SIPA1	ENST00000534313.6 linkuse as main transcript	c.1026G>A	p.Ala342=	synonymous_variant	5/16	1	NM_006747.4	P1
SIPA1	ENST00000394224.3 linkuse as main transcript	c.1026G>A	p.Ala342=	synonymous_variant	5/16	1		P1
SIPA1	ENST00000527525.5 linkuse as main transcript	c.1026G>A	p.Ala342=	synonymous_variant	5/17	2

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59835

AN:

151828

Hom.:

12285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.441

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.501

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.377

GnomAD3 exomes

AF:

0.394

AC:

98796

AN:

251014

Hom.:

21044

AF XY:

0.408

AC XY:

55331

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.197

Gnomad ASJ exome

AF:

0.436

Gnomad EAS exome

AF:

0.253

Gnomad SAS exome

AF:

0.507

Gnomad FIN exome

AF:

0.526

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.406

GnomAD4 exome

AF:

0.413

AC:

603003

AN:

1461462

Hom.:

127695

Cov.:

AF XY:

0.417

AC XY:

303356

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.346

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.435

Gnomad4 EAS exome

AF:

0.210

Gnomad4 SAS exome

AF:

0.507

Gnomad4 FIN exome

AF:

0.517

Gnomad4 NFE exome

AF:

0.418

Gnomad4 OTH exome

AF:

0.406

GnomAD4 genome

AF:

0.394

AC:

59879

AN:

151946

Hom.:

12293

Cov.:

AF XY:

0.400

AC XY:

29656

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.346

Gnomad4 AMR

AF:

0.285

Gnomad4 ASJ

AF:

0.441

Gnomad4 EAS

AF:

0.245

Gnomad4 SAS

AF:

0.501

Gnomad4 FIN

AF:

0.545

Gnomad4 NFE

AF:

0.427

Gnomad4 OTH

AF:

0.382

Alfa

AF:

0.400

Hom.:

14255

Bravo

AF:

0.365

Asia WGS

AF:

0.347

AC:

1205

AN:

3478

EpiCase

AF:

0.427

EpiControl

AF:

0.431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.29

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over