chr14-24964647-C-CTGTGTGTGTGTGTG

Variant names:

• chr14-24964647-C-CTGTGTGTGTGTGTG
• rs34132743
• NM_001394410.1:c.154+10004_154+10017dupCACACACACACACA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001394410.1(STXBP6):​c.154+10004_154+10017dupCACACACACACACA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.074 (396 hom., cov: 0)
• Consequence: STXBP6 NM_001394410.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450
• Publications: 1 publications found

Genes affected

STXBP6 (HGNC:19666): (syntaxin binding protein 6) Enables cadherin binding activity involved in cell-cell adhesion. Predicted to be involved in Golgi to plasma membrane transport and exocytosis. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP6	NM_001394410.1	c.154+10004_154+10017dupCACACACACACACA		intron_variant	Intron 2 of 5	ENST00000323944.10	NP_001381339.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP6	ENST00000323944.10	c.154+10017_154+10018insCACACACACACACA		intron_variant	Intron 2 of 5	1	NM_001394410.1	ENSP00000324302.5

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 10364 AN: 139878 Hom.: 398 Cov.: 0

Gnomad AFR AF: 0.0576

Gnomad AMI AF: 0.0225

Gnomad AMR AF: 0.0901

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.0757

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0574

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0801

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

GnomAD4 genome AF: 0.0741 AC: 10373 AN: 139960 Hom.: 396 Cov.: 0 AF XY: 0.0739 AC XY: 4989 AN XY: 67496

African (AFR) AF: 0.0576 AC: 2143 AN: 37234

American (AMR) AF: 0.0904 AC: 1257 AN: 13908

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 326 AN: 3328

East Asian (EAS) AF: 0.0812 AC: 387 AN: 4766

South Asian (SAS) AF: 0.0764 AC: 312 AN: 4082

European-Finnish (FIN) AF: 0.0808 AC: 723 AN: 8950

Middle Eastern (MID) AF: 0.0588 AC: 16 AN: 272

European-Non Finnish (NFE) AF: 0.0779 AC: 5035 AN: 64622

Other (OTH) AF: 0.0807 AC: 154 AN: 1908

Alfa AF: 0.0362 Hom.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.045
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs34132743; hg19: chr14-25433853; COSMIC: COSV60591444;