1-232407960-C-T

Variant names:

• chr1-232407960-C-T
• rs10495322
• NM_020808.5:c.4763-3782G>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.4763-3782G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 152,214 control chromosomes in the GnomAD database, including 743 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 0.035 (743 hom., cov: 32)
• Consequence: SIPA1L2 NM_020808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 1 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1L2	NM_020808.5	c.4763-3782G>A		intron_variant	Intron 19 of 22	ENST00000674635.1	NP_065859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1L2	ENST00000674635.1	c.4763-3782G>A		intron_variant	Intron 19 of 22		NM_020808.5	ENSP00000502693.1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5260 AN: 152096 Hom.: 744 Cov.: 32

Gnomad AFR AF: 0.00413

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0796

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.0980

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00664

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0346 AC: 5262 AN: 152214 Hom.: 743 Cov.: 32 AF XY: 0.0407 AC XY: 3028 AN XY: 74442

African (AFR) AF: 0.00412 AC: 171 AN: 41542

American (AMR) AF: 0.0801 AC: 1223 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3468

East Asian (EAS) AF: 0.480 AC: 2479 AN: 5162

South Asian (SAS) AF: 0.0981 AC: 473 AN: 4824

European-Finnish (FIN) AF: 0.0339 AC: 360 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00663 AC: 451 AN: 68026

Other (OTH) AF: 0.0284 AC: 60 AN: 2110

Alfa AF: 0.0183 Hom.: 18

Bravo AF: 0.0377

Asia WGS AF: 0.230 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.5
DANN	Benign	0.81
PhyloP100		0.13
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: rs10495322; hg19: chr1-232543706;