1-232620280-T-C

Position:

• chr1-232620280-T-C

Variant summary

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

The NM_020808.5(SIPA1L2):​c.-319+9589A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 152,268 control chromosomes in the GnomAD database, including 378 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 0.030 (378 hom., cov: 33)
• Consequence: SIPA1L2 NM_020808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L2	NM_020808.5	c.-319+9589A>G		intron_variant		ENST00000674635.1	NP_065859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIPA1L2	ENST00000674635.1	c.-319+9589A>G		intron_variant			NM_020808.5	ENSP00000502693	A1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4611 AN: 152148 Hom.: 381 Cov.: 33

Gnomad AFR AF: 0.00673

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.0331

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0258

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

GnomAD4 genome AF: 0.0302 AC: 4603 AN: 152268 Hom.: 378 Cov.: 33 AF XY: 0.0323 AC XY: 2405 AN XY: 74450

Gnomad4 AFR AF: 0.00671

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.0365

Gnomad4 FIN AF: 0.0331

Gnomad4 NFE AF: 0.0225

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0207 Hom.: 17

Bravo AF: 0.0309

Asia WGS AF: 0.176 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.026
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10495332; hg19: chr1-232756026;