rs72752811

Variant names:

• chr9-127690513-G-A
• rs72752811
• NM_003165.6:c.*17-262G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001032221.6(STXBP1):​c.1703-262G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 539,606 control chromosomes in the GnomAD database, including 316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (80 hom., cov: 32)
  • Exomes 𝑓: 0.032 (236 hom.)
• Consequence: STXBP1 NM_001032221.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0980
• Publications: 0 publications found

Genes affected

STXBP1 (HGNC:11444): (syntaxin binding protein 1) This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

PTRH1 (HGNC:27039): (peptidyl-tRNA hydrolase 1 homolog) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000279571 (HGNC:):

MIR3911 (HGNC:38962): (microRNA 3911) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-127690513-G-A is Benign according to our data. Variant chr9-127690513-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1190332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0294 (4476/152306) while in subpopulation NFE AF = 0.0397 (2698/68032). AF 95% confidence interval is 0.0384. There are 80 homozygotes in GnomAd4. There are 2166 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 80 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032221.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP1	NM_003165.6	MANE Plus Clinical	c.*17-262G>A		intron	N/A	NP_003156.1	P61764-2
	STXBP1	NM_001032221.6	MANE Select	c.1703-262G>A		intron	N/A	NP_001027392.1	P61764-1
	STXBP1	NM_001374306.2		c.1694-262G>A		intron	N/A	NP_001361235.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP1	ENST00000373302.8	TSL:1 MANE Plus Clinical	c.*17-262G>A		intron	N/A	ENSP00000362399.3	P61764-2
	STXBP1	ENST00000373299.5	TSL:1 MANE Select	c.1703-262G>A		intron	N/A	ENSP00000362396.2	P61764-1
	PTRH1	ENST00000641641.1		c.*237C>T		3_prime_UTR	Exon 2 of 2	ENSP00000492921.1	A0A286YER0

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4476 AN: 152188 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0364

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0258

GnomAD4 exome AF: 0.0317 AC: 12290 AN: 387300 Hom.: 236 Cov.: 0 AF XY: 0.0318 AC XY: 6531 AN XY: 205170

African (AFR) AF: 0.0130 AC: 144 AN: 11052

American (AMR) AF: 0.0305 AC: 512 AN: 16788

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 271 AN: 11730

East Asian (EAS) AF: 0.00169 AC: 43 AN: 25468

South Asian (SAS) AF: 0.0277 AC: 1254 AN: 45210

European-Finnish (FIN) AF: 0.0293 AC: 700 AN: 23852

Middle Eastern (MID) AF: 0.0121 AC: 20 AN: 1656

European-Non Finnish (NFE) AF: 0.0379 AC: 8697 AN: 229488

Other (OTH) AF: 0.0294 AC: 649 AN: 22056

GnomAD4 genome AF: 0.0294 AC: 4476 AN: 152306 Hom.: 80 Cov.: 32 AF XY: 0.0291 AC XY: 2166 AN XY: 74470

African (AFR) AF: 0.0143 AC: 595 AN: 41558

American (AMR) AF: 0.0365 AC: 559 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3472

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5184

South Asian (SAS) AF: 0.0304 AC: 147 AN: 4830

European-Finnish (FIN) AF: 0.0227 AC: 241 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0397 AC: 2698 AN: 68032

Other (OTH) AF: 0.0256 AC: 54 AN: 2112

Alfa AF: 0.0323 Hom.: 32

Bravo AF: 0.0285

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.33
PhyloP100		-0.098
Mutation Taster		=100/0	polymorphism

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: rs72752811; hg19: chr9-130452792;