rs4649372

Variant names:

• chr1-232443851-T-A
• rs4649372
• NM_020808.5:c.3354-166A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-232443851-T-A
• chr1-232443851-T-G

Variant summary

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

The NM_020808.5(SIPA1L2):​c.3354-166A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,076 control chromosomes in the GnomAD database, including 8,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.31 (8186 hom., cov: 32)
• Consequence: SIPA1L2 NM_020808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 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.3354-166A>T		intron	N/A	NP_065859.3	Q9P2F8-1
	SIPA1L2	NM_001377488.1		c.3354-166A>T		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.3354-166A>T		intron	N/A	ENSP00000502693.1	Q9P2F8-1
	SIPA1L2	ENST00000676213.1		c.3354-166A>T		intron	N/A	ENSP00000501897.1	A0A6Q8PFQ0
	SIPA1L2	ENST00000964479.1		c.3354-166A>T		intron	N/A	ENSP00000634538.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47426 AN: 151958 Hom.: 8171 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.312 AC: 47501 AN: 152076 Hom.: 8186 Cov.: 32 AF XY: 0.316 AC XY: 23515 AN XY: 74328

African (AFR) AF: 0.381 AC: 15810 AN: 41462

American (AMR) AF: 0.432 AC: 6593 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 498 AN: 3472

East Asian (EAS) AF: 0.559 AC: 2889 AN: 5164

South Asian (SAS) AF: 0.367 AC: 1770 AN: 4822

European-Finnish (FIN) AF: 0.236 AC: 2498 AN: 10570

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16564 AN: 67996

Other (OTH) AF: 0.286 AC: 605 AN: 2112

Alfa AF: 0.272 Hom.: 745

Bravo AF: 0.331

Asia WGS AF: 0.393 AC: 1365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		0.25
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: rs4649372; hg19: chr1-232579597; COSMIC: COSV53386269;