rs1156287

chr17-54999438-G-A

Variant summary

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

The NM_178509.6(STXBP4):c.274G>A(p.Gly92Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 1,610,254 control chromosomes in the GnomAD database, including 442,597 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.79 (48226 hom., cov: 31)
  • Exomes 𝑓: 0.73 (394371 hom.)
• Consequence: STXBP4 NM_178509.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

Genes affected

STXBP4 (HGNC:19694): (syntaxin binding protein 4) Enables syntaxin binding activity. Involved in several processes, including positive regulation of cell cycle G1/S phase transition; positive regulation of keratinocyte proliferation; and protein stabilization. Located in extracellular exosome. [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 (MetaRNN=6.621848E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP4	NM_178509.6	c.274G>A	p.Gly92Arg	missense_variant	5/18	ENST00000376352.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP4	ENST00000376352.6	c.274G>A	p.Gly92Arg	missense_variant	5/18	2	NM_178509.6	P1
STXBP4	ENST00000434978.6	c.274G>A	p.Gly92Arg	missense_variant	5/17	1
STXBP4	ENST00000398391.6	c.43G>A	p.Gly15Arg	missense_variant	4/11	1
STXBP4	ENST00000405898.5	c.274G>A	p.Gly92Arg	missense_variant	4/11	5

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120191 AN: 151962 Hom.: 48165 Cov.: 31

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.759

GnomAD3 exomes AF: 0.778 AC: 193669 AN: 248784 Hom.: 76248 AF XY: 0.773 AC XY: 103845 AN XY: 134290

Gnomad AFR exome AF: 0.919

Gnomad AMR exome AF: 0.859

Gnomad ASJ exome AF: 0.769

Gnomad EAS exome AF: 0.894

Gnomad SAS exome AF: 0.809

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.719

Gnomad OTH exome AF: 0.753

GnomAD4 exome AF: 0.733 AC: 1068277 AN: 1458176 Hom.: 394371 Cov.: 35 AF XY: 0.735 AC XY: 532872 AN XY: 725294

Gnomad4 AFR exome AF: 0.924

Gnomad4 AMR exome AF: 0.855

Gnomad4 ASJ exome AF: 0.769

Gnomad4 EAS exome AF: 0.928

Gnomad4 SAS exome AF: 0.812

Gnomad4 FIN exome AF: 0.723

Gnomad4 NFE exome AF: 0.708

Gnomad4 OTH exome AF: 0.744

GnomAD4 genome AF: 0.791 AC: 120315 AN: 152078 Hom.: 48226 Cov.: 31 AF XY: 0.792 AC XY: 58820 AN XY: 74306

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.908

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.759

Alfa AF: 0.738 Hom.: 106136

Bravo AF: 0.803

TwinsUK AF: 0.722 AC: 2676

ALSPAC AF: 0.711 AC: 2740

ESP6500AA AF: 0.906 AC: 3992

ESP6500EA AF: 0.717 AC: 6164

ExAC AF: 0.780 AC: 94697

Asia WGS AF: 0.860 AC: 2984 AN: 3472

EpiCase AF: 0.713

EpiControl AF: 0.718

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	8.8
Dann	Benign	0.15
DEOGEN2	Benign	0.0025	T;T;T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.092	T;T;T;T
MetaRNN	Benign	6.6e-7	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.3	N;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.44	T
PROVEAN	Benign	4.7	N;N;N;N
REVEL	Benign	0.064
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.12
MutPred		0.53		Gain of MoRF binding (P = 0.0072);Gain of MoRF binding (P = 0.0072);Gain of MoRF binding (P = 0.0072);.;
MPC		0.18
ClinPred		0.0019	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.44

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: rs1156287; hg19: chr17-53076799; COSMIC: COSV54842818; COSMIC: COSV54842818;