rs573140

Positions:

• chr1-232441535-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020808.5(SIPA1L2):​c.3539-141A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 807,944 control chromosomes in the GnomAD database, including 30,140 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 0.25 (4958 hom., cov: 32)
  • Exomes 𝑓: 0.27 (25182 hom.)
• Consequence: SIPA1L2 NM_020808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.48

Genes affected

SIPA1L2 (HGNC:23800): (signal induced proliferation associated 1 like 2) This gene encodes a member of the signal-induced proliferation-associated 1 like family. Members of this family contain a GTPase activating domain, a PDZ domain and a C-terminal coiled-coil domain with a leucine zipper. A similar protein in rat acts as a GTPases for the small GTPase Rap. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L2	NM_020808.5	c.3539-141A>C		intron_variant		ENST00000674635.1	NP_065859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIPA1L2	ENST00000674635.1	c.3539-141A>C		intron_variant			NM_020808.5	ENSP00000502693	A1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37826 AN: 151952 Hom.: 4956 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.269 AC: 176316 AN: 655874 Hom.: 25182 AF XY: 0.268 AC XY: 94510 AN XY: 352830

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.294

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.249 AC: 37839 AN: 152070 Hom.: 4958 Cov.: 32 AF XY: 0.247 AC XY: 18389 AN XY: 74354

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.240

Alfa AF: 0.276 Hom.: 1320

Bravo AF: 0.235

Asia WGS AF: 0.162 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0070
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs573140; hg19: chr1-232577281;