chr17-54985542-C-A

Variant names:

• chr17-54985542-C-A
• rs10468513
• NM_178509.6:c.-156-72C>A

Variant summary

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

The NM_001398481.1(STXBP4):​c.-156-72C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,034 control chromosomes in the GnomAD database, including 6,248 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 0.28 (6248 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: STXBP4 NM_001398481.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 7 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 (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001398481.1. 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
	STXBP4	NM_178509.6	MANE Select	c.-156-72C>A		intron	N/A	NP_848604.3
	STXBP4	NM_001398481.1		c.-156-72C>A		intron	N/A	NP_001385410.1
	STXBP4	NM_001398483.1		c.-156-72C>A		intron	N/A	NP_001385412.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP4	ENST00000376352.6	TSL:2 MANE Select	c.-156-72C>A		intron	N/A	ENSP00000365530.2
	STXBP4	ENST00000434978.6	TSL:1	c.-156-72C>A		intron	N/A	ENSP00000391087.2
	STXBP4	ENST00000398391.6	TSL:1	c.-254-72C>A		intron	N/A	ENSP00000381427.2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42679 AN: 151916 Hom.: 6250 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0930

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.281 AC: 42692 AN: 152034 Hom.: 6248 Cov.: 32 AF XY: 0.278 AC XY: 20622 AN XY: 74304

African (AFR) AF: 0.352 AC: 14590 AN: 41458

American (AMR) AF: 0.230 AC: 3514 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3472

East Asian (EAS) AF: 0.0925 AC: 479 AN: 5180

South Asian (SAS) AF: 0.169 AC: 813 AN: 4814

European-Finnish (FIN) AF: 0.275 AC: 2904 AN: 10552

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18771 AN: 67952

Other (OTH) AF: 0.292 AC: 617 AN: 2114

Alfa AF: 0.276 Hom.: 2557

Bravo AF: 0.282

Asia WGS AF: 0.152 AC: 531 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.61
PhyloP100		0.13
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: rs10468513; hg19: chr17-53062903;