rs11156654

chr14-31014749-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083893.2(STRN3):c.282+11155A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 441,822 control chromosomes in the GnomAD database, including 13,059 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 0.25 (5002 hom., cov: 29)
  • Exomes 𝑓: 0.22 (8057 hom.)
• Consequence: STRN3 NM_001083893.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

Genes affected

STRN3 (HGNC:15720): (striatin 3) Enables armadillo repeat domain binding activity; protein phosphatase 2A binding activity; and small GTPase binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; nucleoplasm; and plasma membrane. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]

MIR624 (HGNC:32880): (microRNA 624) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRN3	NM_001083893.2	c.282+11155A>T		intron_variant		ENST00000357479.10
MIR624	NR_030354.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRN3	ENST00000357479.10	c.282+11155A>T		intron_variant		5	NM_001083893.2	P3
STRN3	ENST00000355683.9	c.282+11155A>T		intron_variant		1		A1
STRN3	ENST00000555358.5	c.282+11155A>T		intron_variant, NMD_transcript_variant		1
MIR624	ENST00000385217.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37811 AN: 151436 Hom.: 5001 Cov.: 29

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.235

GnomAD3 exomes AF: 0.204 AC: 26296 AN: 129210 Hom.: 3086 AF XY: 0.201 AC XY: 13793 AN XY: 68558

Gnomad AFR exome AF: 0.292

Gnomad AMR exome AF: 0.122

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.00140

Gnomad SAS exome AF: 0.148

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.248

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.222 AC: 64583 AN: 290270 Hom.: 8057 Cov.: 0 AF XY: 0.218 AC XY: 36073 AN XY: 165456

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.250 AC: 37826 AN: 151552 Hom.: 5002 Cov.: 29 AF XY: 0.246 AC XY: 18191 AN XY: 74040

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.232

Alfa AF: 0.258 Hom.: 1690

Bravo AF: 0.243

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.3
Dann	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs11156654; hg19: chr14-31483955; COSMIC: COSV62581230; COSMIC: COSV62581230;