rs2306364

Variant names:

• chr11-65644996-G-A
• rs2306364
• NM_006747.4:c.1026G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-65644996-G-A
• chr11-65644996-G-C
• chr11-65644996-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006747.4(SIPA1):​c.1026G>A​(p.Ala342Ala) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.71
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SIPA1	NM_006747.4	c.1026G>A	p.Ala342Ala	synonymous_variant	Exon 5 of 16	ENST00000534313.6	NP_006738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1	ENST00000534313.6	c.1026G>A	p.Ala342Ala	synonymous_variant	Exon 5 of 16	1	NM_006747.4	ENSP00000436269.1
SIPA1	ENST00000394224.4	c.1026G>A	p.Ala342Ala	synonymous_variant	Exon 5 of 16	1		ENSP00000377771.3
SIPA1	ENST00000527525.5	c.1026G>A	p.Ala342Ala	synonymous_variant	Exon 5 of 17	2		ENSP00000433686.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59835 AN: 151828 Hom.: 12285 Cov.: 32

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

GnomAD2 exomes AF: 0.394 AC: 98796 AN: 251014 AF XY: 0.408

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 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.: 47 AF XY: 0.417 AC XY: 303356 AN XY: 727056

African (AFR) AF: 0.346 AC: 11589 AN: 33476

American (AMR) AF: 0.206 AC: 9201 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 11358 AN: 26120

East Asian (EAS) AF: 0.210 AC: 8323 AN: 39692

South Asian (SAS) AF: 0.507 AC: 43772 AN: 86256

European-Finnish (FIN) AF: 0.517 AC: 27614 AN: 53412

Middle Eastern (MID) AF: 0.425 AC: 2452 AN: 5766

European-Non Finnish (NFE) AF: 0.418 AC: 464202 AN: 1111678

Other (OTH) AF: 0.406 AC: 24492 AN: 60370

GnomAD4 genome AF: 0.394 AC: 59879 AN: 151946 Hom.: 12293 Cov.: 32 AF XY: 0.400 AC XY: 29656 AN XY: 74232

African (AFR) AF: 0.346 AC: 14328 AN: 41420

American (AMR) AF: 0.285 AC: 4359 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1529 AN: 3468

East Asian (EAS) AF: 0.245 AC: 1267 AN: 5170

South Asian (SAS) AF: 0.501 AC: 2410 AN: 4810

European-Finnish (FIN) AF: 0.545 AC: 5754 AN: 10558

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29004 AN: 67946

Other (OTH) AF: 0.382 AC: 802 AN: 2102

Alfa AF: 0.396 Hom.: 17320

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
PhyloP100		-7.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs2306364; hg19: chr11-65412467; COSMIC: COSV67746799; COSMIC: COSV67746799;