rs1156287

Variant names:

• chr17-54999438-G-A
• rs1156287
• NM_178509.6:c.274G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 48 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178509.6. 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
	STXBP4	NM_178509.6	MANE Select	c.274G>A	p.Gly92Arg	missense	Exon 5 of 18	NP_848604.3
	STXBP4	NM_001398481.1		c.274G>A	p.Gly92Arg	missense	Exon 5 of 18	NP_001385410.1
	STXBP4	NM_001398483.1		c.274G>A	p.Gly92Arg	missense	Exon 5 of 17	NP_001385412.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP4	ENST00000376352.6	TSL:2 MANE Select	c.274G>A	p.Gly92Arg	missense	Exon 5 of 18	ENSP00000365530.2
	STXBP4	ENST00000434978.6	TSL:1	c.274G>A	p.Gly92Arg	missense	Exon 5 of 17	ENSP00000391087.2
	STXBP4	ENST00000398391.6	TSL:1	c.43G>A	p.Gly15Arg	missense	Exon 4 of 11	ENSP00000381427.2

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

GnomAD2 exomes AF: 0.778 AC: 193669 AN: 248784 AF XY: 0.773

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 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

African (AFR) AF: 0.924 AC: 30824 AN: 33348

American (AMR) AF: 0.855 AC: 37883 AN: 44330

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 20031 AN: 26040

East Asian (EAS) AF: 0.928 AC: 36746 AN: 39578

South Asian (SAS) AF: 0.812 AC: 69380 AN: 85450

European-Finnish (FIN) AF: 0.723 AC: 38586 AN: 53376

Middle Eastern (MID) AF: 0.772 AC: 4446 AN: 5758

European-Non Finnish (NFE) AF: 0.708 AC: 785526 AN: 1110024

Other (OTH) AF: 0.744 AC: 44855 AN: 60272

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

African (AFR) AF: 0.913 AC: 37919 AN: 41510

American (AMR) AF: 0.799 AC: 12204 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2642 AN: 3470

East Asian (EAS) AF: 0.908 AC: 4706 AN: 5184

South Asian (SAS) AF: 0.826 AC: 3985 AN: 4822

European-Finnish (FIN) AF: 0.726 AC: 7650 AN: 10536

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48599 AN: 67970

Other (OTH) AF: 0.759 AC: 1603 AN: 2112

Alfa AF: 0.742 Hom.: 194875

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 v4.9

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
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.092	T
MetaRNN	Benign	6.6e-7	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.3	N
PhyloP100		2.0
PrimateAI	Benign	0.44	T
PROVEAN	Benign	4.7	N
REVEL	Benign	0.064
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.53		Gain of MoRF binding (P = 0.0072)
MPC		0.18
ClinPred		0.0019	T
GERP RS		3.6
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.44
Mutation Taster		=98/2	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: rs1156287; hg19: chr17-53076799; COSMIC: COSV54842818; COSMIC: COSV54842818;