chr14-71590638-G-A

Position:

• chr14-71590638-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386936.1(SIPA1L1):​c.1498+1268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,144 control chromosomes in the GnomAD database, including 51,271 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 0.82 (51271 hom., cov: 31)
• Consequence: SIPA1L1 NM_001386936.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIPA1L1	NM_001386936.1	c.1498+1268G>A		intron_variant		ENST00000381232.8	NP_001373865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIPA1L1	ENST00000381232.8	c.1498+1268G>A		intron_variant		1	NM_001386936.1	ENSP00000370630	P4
SIPA1L1	ENST00000555818.5	c.1498+1268G>A		intron_variant		1		ENSP00000450832
SIPA1L1	ENST00000358550.6	c.1498+1268G>A		intron_variant		2		ENSP00000351352	A1

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124147 AN: 152026 Hom.: 51215 Cov.: 31

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.817 AC: 124264 AN: 152144 Hom.: 51271 Cov.: 31 AF XY: 0.820 AC XY: 61002 AN XY: 74366

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.704

Gnomad4 EAS AF: 0.913

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.784

Alfa AF: 0.754 Hom.: 93992

Bravo AF: 0.818

Asia WGS AF: 0.877 AC: 3049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.042
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs11848785; hg19: chr14-72057355;