rs2448490

Variant names:

• chr11-65644564-G-A
• rs2448490
• NM_006747.4:c.985-391G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-65644564-G-A
• chr11-65644564-G-C
• chr11-65644564-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006747.4(SIPA1):​c.985-391G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,636 control chromosomes in the GnomAD database, including 6,460 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 0.28 (6460 hom., cov: 29)
• Consequence: SIPA1 NM_006747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 26 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1	NM_006747.4	c.985-391G>A		intron_variant	Intron 4 of 15	ENST00000534313.6	NP_006738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1	ENST00000534313.6	c.985-391G>A		intron_variant	Intron 4 of 15	1	NM_006747.4	ENSP00000436269.1
SIPA1	ENST00000394224.4	c.985-391G>A		intron_variant	Intron 4 of 15	1		ENSP00000377771.3
SIPA1	ENST00000527525.5	c.985-391G>A		intron_variant	Intron 4 of 16	2		ENSP00000433686.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41748 AN: 151516 Hom.: 6463 Cov.: 29

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.313

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.275 AC: 41745 AN: 151636 Hom.: 6460 Cov.: 29 AF XY: 0.266 AC XY: 19746 AN XY: 74100

African (AFR) AF: 0.157 AC: 6495 AN: 41328

American (AMR) AF: 0.264 AC: 4021 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3468

East Asian (EAS) AF: 0.261 AC: 1339 AN: 5134

South Asian (SAS) AF: 0.133 AC: 637 AN: 4796

European-Finnish (FIN) AF: 0.251 AC: 2638 AN: 10518

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24352 AN: 67838

Other (OTH) AF: 0.308 AC: 648 AN: 2102

Alfa AF: 0.321 Hom.: 10568

Bravo AF: 0.275

Asia WGS AF: 0.168 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.46
PhyloP100		-1.8
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: rs2448490; hg19: chr11-65412035;