chr14-71727684-C-T

Variant names:

• chr14-71727684-C-T
• rs17100926
• NM_001386936.1:c.4615-2371C>T

Variant summary

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

The NM_001386936.1(SIPA1L1):​c.4615-2371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 152,268 control chromosomes in the GnomAD database, including 721 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 0.090 (721 hom., cov: 32)
• Consequence: SIPA1L1 NM_001386936.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386936.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1L1	NM_001386936.1	MANE Select	c.4615-2371C>T		intron	N/A	NP_001373865.1
	SIPA1L1	NM_001354285.2		c.4678-2371C>T		intron	N/A	NP_001341214.1
	SIPA1L1	NM_015556.4		c.4678-2371C>T		intron	N/A	NP_056371.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIPA1L1	ENST00000381232.8	TSL:1 MANE Select	c.4615-2371C>T		intron	N/A	ENSP00000370630.3
	SIPA1L1	ENST00000555818.5	TSL:1	c.4678-2371C>T		intron	N/A	ENSP00000450832.1
	SIPA1L1	ENST00000358550.6	TSL:2	c.4615-2371C>T		intron	N/A	ENSP00000351352.2

Frequencies

GnomAD3 genomes AF: 0.0899 AC: 13681 AN: 152150 Hom.: 721 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0721

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0543

Gnomad SAS AF: 0.0635

Gnomad FIN AF: 0.0359

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.0984

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

GnomAD4 genome AF: 0.0898 AC: 13681 AN: 152268 Hom.: 721 Cov.: 32 AF XY: 0.0870 AC XY: 6475 AN XY: 74442

African (AFR) AF: 0.130 AC: 5416 AN: 41544

American (AMR) AF: 0.0719 AC: 1101 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3470

East Asian (EAS) AF: 0.0540 AC: 279 AN: 5166

South Asian (SAS) AF: 0.0632 AC: 305 AN: 4828

European-Finnish (FIN) AF: 0.0359 AC: 381 AN: 10618

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0797 AC: 5422 AN: 68016

Other (OTH) AF: 0.0974 AC: 206 AN: 2116

Alfa AF: 0.0836 Hom.: 1166

Bravo AF: 0.0946

Asia WGS AF: 0.0660 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.27
DANN	Benign	0.64
PhyloP100		-0.60
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: rs17100926; hg19: chr14-72194401;