chr11-65649963-G-A

Variant names:

• chr11-65649963-G-A
• rs746429
• NM_006747.4:c.2760G>A

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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.70
• Publications: 35 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=-0.86).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006747.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1	NM_006747.4	MANE Select	c.2760G>A	p.Ala920Ala	synonymous	Exon 13 of 16	NP_006738.3
	SIPA1	NM_153253.30		c.2760G>A	p.Ala920Ala	synonymous	Exon 13 of 16	NP_694985.29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1	ENST00000534313.6	TSL:1 MANE Select	c.2760G>A	p.Ala920Ala	synonymous	Exon 13 of 16	ENSP00000436269.1
	SIPA1	ENST00000394224.4	TSL:1	c.2760G>A	p.Ala920Ala	synonymous	Exon 13 of 16	ENSP00000377771.3
	SIPA1	ENST00000969242.1		c.2859G>A	p.Ala953Ala	synonymous	Exon 14 of 17	ENSP00000639301.1

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

GnomAD2 exomes AF: 0.310 AC: 77864 AN: 251176 AF XY: 0.320

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

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

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

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: 89 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24257 AN: 67948

Other (OTH) AF: 0.283 AC: 596 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.059
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)

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

Other links and lift over

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