rs3855981

Variant names:

• chr1-232547857-G-A
• rs3855981
• NM_020808.5:c.-270+26317C>T

Variant summary

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

The NM_020808.5(SIPA1L2):​c.-270+26317C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,840 control chromosomes in the GnomAD database, including 24,666 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 0.57 (24666 hom., cov: 31)
• Consequence: SIPA1L2 NM_020808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020808.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1L2	NM_020808.5	MANE Select	c.-270+26317C>T		intron	N/A	NP_065859.3
	SIPA1L2	NM_001377488.1		c.-270+26317C>T		intron	N/A	NP_001364417.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1L2	ENST00000674635.1	MANE Select	c.-270+26317C>T		intron	N/A	ENSP00000502693.1
	SIPA1L2	ENST00000676213.1		c.-269-32249C>T		intron	N/A	ENSP00000501897.1
	SIPA1L2	ENST00000366630.5	TSL:5	c.-270+13612C>T		intron	N/A	ENSP00000355589.1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85953 AN: 151720 Hom.: 24647 Cov.: 31

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.567 AC: 86021 AN: 151840 Hom.: 24666 Cov.: 31 AF XY: 0.571 AC XY: 42357 AN XY: 74210

African (AFR) AF: 0.525 AC: 21742 AN: 41376

American (AMR) AF: 0.550 AC: 8388 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1950 AN: 3470

East Asian (EAS) AF: 0.659 AC: 3396 AN: 5154

South Asian (SAS) AF: 0.648 AC: 3111 AN: 4798

European-Finnish (FIN) AF: 0.635 AC: 6689 AN: 10542

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.575 AC: 39041 AN: 67942

Other (OTH) AF: 0.539 AC: 1135 AN: 2106

Alfa AF: 0.571 Hom.: 10687

Bravo AF: 0.558

Asia WGS AF: 0.611 AC: 2127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.17
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3855981; hg19: chr1-232683603;