rs1990673

Variant names:

• chr17-54972664-C-T
• rs1990673
• NM_178509.6:c.-157+3849C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.91).
• 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 rank	MANE	Protein	UniProt
STXBP4	NM_178509.6	c.-157+3849C>T		intron_variant	Intron 1 of 17	ENST00000376352.6	NP_848604.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP4	ENST00000376352.6	c.-157+3849C>T		intron_variant	Intron 1 of 17	2	NM_178509.6	ENSP00000365530.2

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

African (AFR) AF: 0.811 AC: 33649 AN: 41472

American (AMR) AF: 0.535 AC: 8158 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1679 AN: 3472

East Asian (EAS) AF: 0.465 AC: 2404 AN: 5170

South Asian (SAS) AF: 0.582 AC: 2802 AN: 4814

European-Finnish (FIN) AF: 0.629 AC: 6621 AN: 10518

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40469 AN: 67972

Other (OTH) AF: 0.614 AC: 1294 AN: 2106

Alfa AF: 0.638 Hom.: 4069

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
PhyloP100		-0.10
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: rs1990673; hg19: chr17-53050025;