chr14-24964647-C-CTGTGTGTGTG

Variant names:

• chr14-24964647-C-CTGTGTGTGTG
• rs34132743
• NM_001394410.1:c.154+10008_154+10017dupCACACACACA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001394410.1(STXBP6):​c.154+10008_154+10017dupCACACACACA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.025 (65 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0252 (3537/140118) while in subpopulation AFR AF = 0.0472 (1758/37260). AF 95% confidence interval is 0.0453. There are 65 homozygotes in GnomAd4. There are 1673 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 65 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP6	NM_001394410.1	c.154+10008_154+10017dupCACACACACA		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+10018insCACACACACA		intron_variant	Intron 2 of 5	1	NM_001394410.1	ENSP00000324302.5

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3525 AN: 140034 Hom.: 65 Cov.: 0

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.00112

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0120

Gnomad EAS AF: 0.0230

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.0236

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0216

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

GnomAD4 genome AF: 0.0252 AC: 3537 AN: 140118 Hom.: 65 Cov.: 0 AF XY: 0.0248 AC XY: 1673 AN XY: 67578

African (AFR) AF: 0.0472 AC: 1758 AN: 37260

American (AMR) AF: 0.0154 AC: 214 AN: 13930

Ashkenazi Jewish (ASJ) AF: 0.0120 AC: 40 AN: 3336

East Asian (EAS) AF: 0.0229 AC: 109 AN: 4768

South Asian (SAS) AF: 0.0139 AC: 57 AN: 4090

European-Finnish (FIN) AF: 0.0241 AC: 216 AN: 8970

Middle Eastern (MID) AF: 0.0221 AC: 6 AN: 272

European-Non Finnish (NFE) AF: 0.0169 AC: 1095 AN: 64692

Other (OTH) AF: 0.0215 AC: 41 AN: 1910

Alfa AF: 0.00 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

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;