rs10871454

Variant names:

• chr16-31036758-C-T
• rs10871454
• NM_004604.5:c.379-1168C>T

Variant summary

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

The NM_004604.5(STX4):​c.379-1168C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,950 control chromosomes in the GnomAD database, including 10,094 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 0.32 (10094 hom., cov: 31)
• Consequence: STX4 NM_004604.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 89 publications found

Genes affected

STX4 (HGNC:11439): (syntaxin 4) Enables sphingomyelin phosphodiesterase activator activity. Involved in several processes, including cornified envelope assembly; positive regulation of immune effector process; and positive regulation of protein localization. Located in several cellular components, including basolateral plasma membrane; cytoplasmic vesicle; and lamellipodium. Part of SNARE complex. Is active in glutamatergic synapse and postsynapse. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX4	NM_004604.5	c.379-1168C>T		intron_variant	Intron 5 of 10	ENST00000313843.8	NP_004595.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX4	ENST00000313843.8	c.379-1168C>T		intron_variant	Intron 5 of 10	1	NM_004604.5	ENSP00000317714.3

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48769 AN: 151832 Hom.: 10095 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.321 AC: 48769 AN: 151950 Hom.: 10094 Cov.: 31 AF XY: 0.324 AC XY: 24035 AN XY: 74260

African (AFR) AF: 0.104 AC: 4297 AN: 41460

American (AMR) AF: 0.393 AC: 5988 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1743 AN: 3462

East Asian (EAS) AF: 0.892 AC: 4610 AN: 5166

South Asian (SAS) AF: 0.177 AC: 854 AN: 4814

European-Finnish (FIN) AF: 0.392 AC: 4131 AN: 10538

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25771 AN: 67956

Other (OTH) AF: 0.388 AC: 819 AN: 2110

Alfa AF: 0.383 Hom.: 56346

Bravo AF: 0.325

Asia WGS AF: 0.461 AC: 1606 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	4.1
DANN	Benign	0.38
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10871454; hg19: chr16-31048079;