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]

STX4 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive 123

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004604.5. 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
	STX4	NM_004604.5	MANE Select	c.379-1168C>T		intron	N/A	NP_004595.2
	STX4	NM_001272096.1		c.373-1168C>T		intron	N/A	NP_001259025.1	Q12846-2
	STX4	NM_001272095.1		c.145-1168C>T		intron	N/A	NP_001259024.1	B7Z425

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX4	ENST00000313843.8	TSL:1 MANE Select	c.379-1168C>T		intron	N/A	ENSP00000317714.3	Q12846-1
	STX4	ENST00000487411.5	TSL:1	n.775-1168C>T		intron	N/A
	STX4	ENST00000927499.1		c.379-1168C>T		intron	N/A	ENSP00000597558.1

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 v4.9

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;