NM_001386936.1:c.-303+5527T>G

Variant names:

• chr14-71534897-T-G
• rs10483836
• NM_001386936.1:c.-303+5527T>G

Variant summary

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

The NM_001386936.1(SIPA1L1):​c.-303+5527T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,242 control chromosomes in the GnomAD database, including 2,653 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 0.16 (2653 hom., cov: 32)
• Consequence: SIPA1L1 NM_001386936.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• Publications: 2 publications found

Genes affected

SIPA1L1 (HGNC:20284): (signal induced proliferation associated 1 like 1) Predicted to enable GTPase activator activity; actin filament binding activity; and protein kinase binding activity. Predicted to be involved in several processes, including actin cytoskeleton organization; activation of GTPase activity; and regulation of postsynapse organization. Located in actin cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIPA1L1	NM_001386936.1	c.-303+5527T>G		intron_variant	Intron 4 of 23	ENST00000381232.8	NP_001373865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIPA1L1	ENST00000381232.8	c.-303+5527T>G		intron_variant	Intron 4 of 23	1	NM_001386936.1	ENSP00000370630.3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24990 AN: 152124 Hom.: 2656 Cov.: 32

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.0637

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.164 AC: 24973 AN: 152242 Hom.: 2653 Cov.: 32 AF XY: 0.160 AC XY: 11903 AN XY: 74436

African (AFR) AF: 0.0490 AC: 2036 AN: 41564

American (AMR) AF: 0.162 AC: 2473 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 888 AN: 3472

East Asian (EAS) AF: 0.0635 AC: 330 AN: 5196

South Asian (SAS) AF: 0.131 AC: 633 AN: 4832

European-Finnish (FIN) AF: 0.163 AC: 1729 AN: 10596

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16044 AN: 67972

Other (OTH) AF: 0.201 AC: 425 AN: 2112

Alfa AF: 0.196 Hom.: 982

Bravo AF: 0.162

Asia WGS AF: 0.0990 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.61
PhyloP100		0.38
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: rs10483836; hg19: chr14-72001614;