dbSNP rs746429: SIPA1:p.Ala920Ala (chr11-65649963-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006747.4(SIPA1):c.2760G>A(p.Ala920Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,613,432 control chromosomes in the GnomAD database, including 93,495 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 0.30 ( 7375 hom., cov: 31)

Exomes 𝑓: 0.34 ( 86120 hom. )

Consequence

SIPA1
NM_006747.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.70

Publications

35 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP7

Synonymous conserved (PhyloP=-5.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1	NM_006747.4 link	c.2760G>A	p.Ala920Ala	synonymous_variant	Exon 13 of 16	ENST00000534313.6	NP_006738.3	Q96FS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1	ENST00000534313.6 link	c.2760G>A	p.Ala920Ala	synonymous_variant	Exon 13 of 16	1	NM_006747.4	ENSP00000436269.1		Q96FS4

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44970

AN:

151862

Hom.:

7378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.496

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.280

GnomAD2 exomes

AF:

0.310

AC:

77864

AN:

251176

AF XY:

0.320

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.331

Gnomad EAS exome

AF:

0.220

Gnomad FIN exome

AF:

0.474

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.322

GnomAD4 exome

AF:

0.337

AC:

491928

AN:

1461452

Hom.:

86120

Cov.:

AF XY:

0.339

AC XY:

246116

AN XY:

727030

show subpopulations

African (AFR)

AF:

0.176

AC:

5895

AN:

33476

American (AMR)

AF:

0.152

AC:

6777

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

8610

AN:

26134

East Asian (EAS)

AF:

0.176

AC:

6968

AN:

39700

South Asian (SAS)

AF:

0.333

AC:

28731

AN:

86252

European-Finnish (FIN)

AF:

0.466

AC:

24828

AN:

53314

Middle Eastern (MID)

AF:

0.293

AC:

1689

AN:

5768

European-Non Finnish (NFE)

AF:

0.350

AC:

389292

AN:

1111698

Other (OTH)

AF:

0.317

AC:

19138

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

18814

37628

56441

75255

94069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.296

AC:

44978

AN:

151980

Hom.:

7375

Cov.:

AF XY:

0.301

AC XY:

22376

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.185

AC:

7653

AN:

41460

American (AMR)

AF:

0.209

AC:

3196

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1147

AN:

3468

East Asian (EAS)

AF:

0.208

AC:

1075

AN:

5162

South Asian (SAS)

AF:

0.316

AC:

1519

AN:

4802

European-Finnish (FIN)

AF:

0.496

AC:

5241

AN:

10558

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.357

AC:

24257

AN:

67948

Other (OTH)

AF:

0.283

AC:

596

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1572

3144

4717

6289

7861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.318

Hom.:

6749

Bravo

AF:

0.267

Asia WGS

AF:

0.236

AC:

822

AN:

3478

EpiCase

AF:

0.354

EpiControl

AF:

0.354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.059

(source)

DANN

Benign

0.83

PhyloP100

-5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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rs746429

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over