1-232432547-A-G

Position:

• chr1-232432547-A-G

Variant summary

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

The NM_020808.5(SIPA1L2):​c.4032-76T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 1,367,762 control chromosomes in the GnomAD database, including 605,953 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 0.95 (69398 hom., cov: 34)
  • Exomes 𝑓: 0.94 (536555 hom.)
• Consequence: SIPA1L2 NM_020808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L2	NM_020808.5	c.4032-76T>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.4032-76T>C		intron_variant			NM_020808.5	ENSP00000502693.1

Frequencies

GnomAD3 genomes AF: 0.954 AC: 145239 AN: 152232 Hom.: 69337 Cov.: 34

Gnomad AFR AF: 0.989

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.944

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.961

GnomAD4 exome AF: 0.939 AC: 1141730 AN: 1215412 Hom.: 536555 AF XY: 0.941 AC XY: 573324 AN XY: 609398

Gnomad4 AFR exome AF: 0.991

Gnomad4 AMR exome AF: 0.978

Gnomad4 ASJ exome AF: 0.947

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.985

Gnomad4 FIN exome AF: 0.917

Gnomad4 NFE exome AF: 0.930

Gnomad4 OTH exome AF: 0.950

GnomAD4 genome AF: 0.954 AC: 145359 AN: 152350 Hom.: 69398 Cov.: 34 AF XY: 0.956 AC XY: 71177 AN XY: 74486

Gnomad4 AFR AF: 0.989

Gnomad4 AMR AF: 0.967

Gnomad4 ASJ AF: 0.944

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.990

Gnomad4 FIN AF: 0.920

Gnomad4 NFE AF: 0.930

Gnomad4 OTH AF: 0.962

Alfa AF: 0.929 Hom.: 13674

Bravo AF: 0.959

Asia WGS AF: 0.993 AC: 3453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.9
DANN	Benign	0.74

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: rs1547741; hg19: chr1-232568293;