rs1990673

chr17-54972664-C-T

Variant summary

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

The NM_178509.6(STXBP4):c.-157+3849C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 151,990 control chromosomes in the GnomAD database, including 32,470 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 0.64 (32470 hom., cov: 32)
• Consequence: STXBP4 NM_178509.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP4	NM_178509.6	c.-157+3849C>T		intron_variant		ENST00000376352.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP4	ENST00000376352.6	c.-157+3849C>T		intron_variant		2	NM_178509.6	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97699 AN: 151872 Hom.: 32431 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.643 AC: 97795 AN: 151990 Hom.: 32470 Cov.: 32 AF XY: 0.641 AC XY: 47623 AN XY: 74294

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.614

Alfa AF: 0.631 Hom.: 3815

Bravo AF: 0.641

Asia WGS AF: 0.571 AC: 1988 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	1.4
Dann	Benign	0.43

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: rs1990673; hg19: chr17-53050025;