rs7219986

Variant names:

• chr17-55185846-C-T
• rs7219986
• XM_047435714.1:c.*9972C>T

Variant summary

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

The XM_047435714.1(STXBP4):​c.*9972C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0809 in 152,010 control chromosomes in the GnomAD database, including 1,050 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 0.081 (1050 hom., cov: 31)
• Consequence: STXBP4 XM_047435714.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607
• Publications: 4 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP4	XM_047435714.1	c.*9972C>T		3_prime_UTR_variant	Exon 18 of 18		XP_047291670.1
STXBP4	XR_007065289.1	n.1965+9777C>T		intron_variant	Intron 18 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0807 AC: 12252 AN: 151892 Hom.: 1038 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0396

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.0522

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0649

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

GnomAD4 genome AF: 0.0809 AC: 12301 AN: 152010 Hom.: 1050 Cov.: 31 AF XY: 0.0809 AC XY: 6011 AN XY: 74308

African (AFR) AF: 0.207 AC: 8585 AN: 41390

American (AMR) AF: 0.0396 AC: 606 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 168 AN: 3470

East Asian (EAS) AF: 0.185 AC: 956 AN: 5160

South Asian (SAS) AF: 0.0518 AC: 249 AN: 4808

European-Finnish (FIN) AF: 0.0222 AC: 235 AN: 10582

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0198 AC: 1346 AN: 67994

Other (OTH) AF: 0.0638 AC: 135 AN: 2116

Alfa AF: 0.0377 Hom.: 493

Bravo AF: 0.0893

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.67
PhyloP100		-0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7219986; hg19: chr17-53263207;