rs746429

Positions:

• chr11-65649963-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006747.4(SIPA1):​c.2760G>A​(p.Ala920=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.70

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SIPA1	NM_006747.4	c.2760G>A	p.Ala920=	synonymous_variant	13/16	ENST00000534313.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIPA1	ENST00000534313.6	c.2760G>A	p.Ala920=	synonymous_variant	13/16	1	NM_006747.4	P1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44970 AN: 151862 Hom.: 7378 Cov.: 31

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

GnomAD3 exomes AF: 0.310 AC: 77864 AN: 251176 Hom.: 13277 AF XY: 0.320 AC XY: 43438 AN XY: 135780

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 SAS exome AF: 0.330

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.: 38 AF XY: 0.339 AC XY: 246116 AN XY: 727030

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.296 AC: 44978 AN: 151980 Hom.: 7375 Cov.: 31 AF XY: 0.301 AC XY: 22376 AN XY: 74278

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.283

Alfa AF: 0.320 Hom.: 6148

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
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs746429; hg19: chr11-65417434; COSMIC: COSV58014624; COSMIC: COSV58014624;