chr1-232432547-A-G

Variant names:

• chr1-232432547-A-G
• rs1547741
• NM_020808.5:c.4032-76T>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.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
• Publications: 3 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1L2	NM_020808.5	MANE Select	c.4032-76T>C		intron	N/A	NP_065859.3	Q9P2F8-1
	SIPA1L2	NM_001377488.1		c.4032-76T>C		intron	N/A	NP_001364417.1	A0A6Q8PH54

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1L2	ENST00000674635.1	MANE Select	c.4032-76T>C		intron	N/A	ENSP00000502693.1	Q9P2F8-1
	SIPA1L2	ENST00000676213.1		c.4185-76T>C		intron	N/A	ENSP00000501897.1	A0A6Q8PFQ0
	SIPA1L2	ENST00000964479.1		c.4185-76T>C		intron	N/A	ENSP00000634538.1

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

African (AFR) AF: 0.991 AC: 28329 AN: 28574

American (AMR) AF: 0.978 AC: 37781 AN: 38630

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 21971 AN: 23208

East Asian (EAS) AF: 1.00 AC: 37683 AN: 37684

South Asian (SAS) AF: 0.985 AC: 74548 AN: 75662

European-Finnish (FIN) AF: 0.917 AC: 46400 AN: 50590

Middle Eastern (MID) AF: 0.989 AC: 5210 AN: 5270

European-Non Finnish (NFE) AF: 0.930 AC: 840267 AN: 903638

Other (OTH) AF: 0.950 AC: 49541 AN: 52156

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

African (AFR) AF: 0.989 AC: 41117 AN: 41590

American (AMR) AF: 0.967 AC: 14807 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.944 AC: 3278 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5176 AN: 5176

South Asian (SAS) AF: 0.990 AC: 4782 AN: 4830

European-Finnish (FIN) AF: 0.920 AC: 9768 AN: 10614

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63263 AN: 68032

Other (OTH) AF: 0.962 AC: 2035 AN: 2116

Alfa AF: 0.938 Hom.: 30029

Bravo AF: 0.959

Asia WGS AF: 0.993 AC: 3453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.9
DANN	Benign	0.74
PhyloP100		0.43
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: rs1547741; hg19: chr1-232568293;