Variant rs75894763 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_006747.4(SIPA1):c.1863G>A(p.Val621Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 1,517,578 control chromosomes in the GnomAD database, including 569 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 0.017 ( 35 hom., cov: 32)

Exomes 𝑓: 0.025 ( 534 hom. )

Consequence

SIPA1
NM_006747.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.851

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP7

Synonymous conserved (PhyloP=-0.851 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0166 (2521/152022) while in subpopulation SAS AF= 0.0319 (154/4824). AF 95% confidence interval is 0.0278. There are 35 homozygotes in gnomad4. There are 1193 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1	NM_006747.4 linkuse as main transcript	c.1863G>A	p.Val621Val	synonymous_variant	8/16	ENST00000534313.6	NP_006738.3	Q96FS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SIPA1	ENST00000534313.6 linkuse as main transcript	c.1863G>A	p.Val621Val	synonymous_variant	8/16	1	NM_006747.4	ENSP00000436269.1	Q96FS4
SIPA1	ENST00000394224.3 linkuse as main transcript	c.1863G>A	p.Val621Val	synonymous_variant	8/16	1		ENSP00000377771.3	Q96FS4
SIPA1	ENST00000527525.5 linkuse as main transcript	c.1630-73G>A		intron_variant		2		ENSP00000433686.1	F6RY50

Frequencies

GnomAD3 genomes

AF:

0.0166

AC:

2519

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00500

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0317

Gnomad FIN

AF:

0.00818

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0256

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0199

AC:

2324

AN:

116494

Hom.:

AF XY:

0.0226

AC XY:

1447

AN XY:

64038

show subpopulations

Gnomad AFR exome

AF:

0.00415

Gnomad AMR exome

AF:

0.0102

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0352

Gnomad FIN exome

AF:

0.00781

Gnomad NFE exome

AF:

0.0263

Gnomad OTH exome

AF:

0.0223

GnomAD4 exome

AF:

0.0246

AC:

33552

AN:

1365556

Hom.:

534

Cov.:

AF XY:

0.0250

AC XY:

16858

AN XY:

673384

show subpopulations

Gnomad4 AFR exome

AF:

0.00398

Gnomad4 AMR exome

AF:

0.0111

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.0000296

Gnomad4 SAS exome

AF:

0.0363

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.0264

Gnomad4 OTH exome

AF:

0.0226

GnomAD4 genome

AF:

0.0166

AC:

2521

AN:

152022

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1193

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00498

Gnomad4 AMR

AF:

0.0158

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0319

Gnomad4 FIN

AF:

0.00818

Gnomad4 NFE

AF:

0.0256

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0195

Hom.:

Bravo

AF:

0.0163

Asia WGS

AF:

0.0120

AC:

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.6

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over