rs10797576

Variant names:

• chr1-232528865-C-T
• rs10797576
• NM_020808.5:c.-269-13257G>A

Variant summary

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

The NM_020808.5(SIPA1L2):​c.-269-13257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,190 control chromosomes in the GnomAD database, including 1,258 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 0.12 (1258 hom., cov: 32)
• Consequence: SIPA1L2 NM_020808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 43 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1L2	NM_020808.5	c.-269-13257G>A		intron_variant	Intron 2 of 22	ENST00000674635.1	NP_065859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1L2	ENST00000674635.1	c.-269-13257G>A		intron_variant	Intron 2 of 22		NM_020808.5	ENSP00000502693.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18528 AN: 152072 Hom.: 1258 Cov.: 32

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0956

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.122 AC: 18534 AN: 152190 Hom.: 1258 Cov.: 32 AF XY: 0.122 AC XY: 9079 AN XY: 74414

African (AFR) AF: 0.0794 AC: 3297 AN: 41536

American (AMR) AF: 0.169 AC: 2586 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3470

East Asian (EAS) AF: 0.140 AC: 722 AN: 5162

South Asian (SAS) AF: 0.133 AC: 639 AN: 4818

European-Finnish (FIN) AF: 0.0956 AC: 1014 AN: 10608

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9084 AN: 67990

Other (OTH) AF: 0.151 AC: 318 AN: 2112

Alfa AF: 0.133 Hom.: 2270

Bravo AF: 0.124

Asia WGS AF: 0.193 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.66
PhyloP100		-1.7
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: rs10797576; hg19: chr1-232664611;