1-232441535-T-G

Variant names:

• chr1-232441535-T-G
• rs573140
• NM_020808.5:c.3539-141A>C

Variant summary

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

The NM_020808.5(SIPA1L2):​c.3539-141A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 807,944 control chromosomes in the GnomAD database, including 30,140 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 0.25 (4958 hom., cov: 32)
  • Exomes 𝑓: 0.27 (25182 hom.)
• Consequence: SIPA1L2 NM_020808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.48
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1L2	NM_020808.5	c.3539-141A>C		intron_variant	Intron 13 of 22	ENST00000674635.1	NP_065859.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1L2	ENST00000674635.1	c.3539-141A>C		intron_variant	Intron 13 of 22		NM_020808.5	ENSP00000502693.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37826 AN: 151952 Hom.: 4956 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.269 AC: 176316 AN: 655874 Hom.: 25182 AF XY: 0.268 AC XY: 94510 AN XY: 352830

African (AFR) AF: 0.185 AC: 3023 AN: 16354

American (AMR) AF: 0.157 AC: 4241 AN: 26996

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 5568 AN: 18944

East Asian (EAS) AF: 0.144 AC: 5154 AN: 35802

South Asian (SAS) AF: 0.230 AC: 14425 AN: 62624

European-Finnish (FIN) AF: 0.306 AC: 11919 AN: 38934

Middle Eastern (MID) AF: 0.258 AC: 1001 AN: 3886

European-Non Finnish (NFE) AF: 0.292 AC: 122071 AN: 418442

Other (OTH) AF: 0.263 AC: 8914 AN: 33892

GnomAD4 genome AF: 0.249 AC: 37839 AN: 152070 Hom.: 4958 Cov.: 32 AF XY: 0.247 AC XY: 18389 AN XY: 74354

African (AFR) AF: 0.188 AC: 7795 AN: 41450

American (AMR) AF: 0.193 AC: 2950 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3470

East Asian (EAS) AF: 0.133 AC: 687 AN: 5176

South Asian (SAS) AF: 0.220 AC: 1062 AN: 4824

European-Finnish (FIN) AF: 0.313 AC: 3314 AN: 10586

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.298 AC: 20274 AN: 67968

Other (OTH) AF: 0.240 AC: 505 AN: 2108

Alfa AF: 0.266 Hom.: 2166

Bravo AF: 0.235

Asia WGS AF: 0.162 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0070
DANN	Benign	0.71
PhyloP100		-3.5
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: rs573140; hg19: chr1-232577281;