rs184013125

Variant names:

• chr1-232425774-G-A
• rs184013125
• NM_020808.5:c.4445C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-232425774-G-A
• chr1-232425774-G-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_020808.5(SIPA1L2):​c.4445C>T​(p.Ser1482Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00742 in 1,613,990 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0077 (46 hom.)
• Consequence: SIPA1L2 NM_020808.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.48
• Publications: 8 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009830773).
• BP6: Variant 1-232425774-G-A is Benign according to our data. Variant chr1-232425774-G-A is described in ClinVar as Benign. ClinVar VariationId is 718930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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.4445C>T	p.Ser1482Leu	missense	Exon 18 of 23	NP_065859.3	Q9P2F8-1
	SIPA1L2	NM_001377488.1		c.4445C>T	p.Ser1482Leu	missense	Exon 18 of 22	NP_001364417.1	A0A6Q8PH54

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1L2	ENST00000674635.1	MANE Select	c.4445C>T	p.Ser1482Leu	missense	Exon 18 of 23	ENSP00000502693.1	Q9P2F8-1
	SIPA1L2	ENST00000676213.1		c.4598C>T	p.Ser1533Leu	missense	Exon 18 of 23	ENSP00000501897.1	A0A6Q8PFQ0
	SIPA1L2	ENST00000964479.1		c.4598C>T	p.Ser1533Leu	missense	Exon 19 of 24	ENSP00000634538.1

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 750 AN: 152198 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00622

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00833

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00557 AC: 1388 AN: 249064 AF XY: 0.00547

Gnomad AFR exome AF: 0.00156

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.000278

Gnomad FIN exome AF: 0.00826

Gnomad NFE exome AF: 0.00918

Gnomad OTH exome AF: 0.00544

GnomAD4 exome AF: 0.00768 AC: 11228 AN: 1461674 Hom.: 46 Cov.: 31 AF XY: 0.00743 AC XY: 5401 AN XY: 727104

African (AFR) AF: 0.00134 AC: 45 AN: 33478

American (AMR) AF: 0.00163 AC: 73 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26122

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.00179 AC: 154 AN: 86202

European-Finnish (FIN) AF: 0.00914 AC: 488 AN: 53402

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5762

European-Non Finnish (NFE) AF: 0.00907 AC: 10087 AN: 1111914

Other (OTH) AF: 0.00556 AC: 336 AN: 60392

GnomAD4 genome AF: 0.00492 AC: 750 AN: 152316 Hom.: 2 Cov.: 33 AF XY: 0.00483 AC XY: 360 AN XY: 74476

African (AFR) AF: 0.00164 AC: 68 AN: 41570

American (AMR) AF: 0.00183 AC: 28 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4826

European-Finnish (FIN) AF: 0.00622 AC: 66 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00833 AC: 567 AN: 68040

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00693 Hom.: 13

Bravo AF: 0.00430

TwinsUK AF: 0.00863 AC: 32

ALSPAC AF: 0.00856 AC: 33

ESP6500AA AF: 0.00233 AC: 10

ESP6500EA AF: 0.00824 AC: 70

ExAC AF: 0.00618 AC: 749

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00709

EpiControl AF: 0.00830

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.031
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0098	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.096
Sift	Uncertain	0.010	D
Sift4G	Benign	0.062	T
Polyphen		0.33	B
Vest4		0.65
MVP		0.093
MPC		0.20
ClinPred		0.028	T
GERP RS		4.8
Varity_R		0.19
gMVP		0.44
Mutation Taster		=98/2	polymorphism

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: rs184013125; hg19: chr1-232561520; COSMIC: COSV99035437;