2-207269271-T-C

Variant names:

• chr2-207269271-T-C
• rs10173558
• ENST00000412387.5:n.316-28933A>G

Variant summary

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

The ENST00000412387.5(MYOSLID-AS1):​n.316-28933A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 532,310 control chromosomes in the GnomAD database, including 12,340 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 0.24 (6030 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6310 hom.)
• Consequence: MYOSLID-AS1 ENST00000412387.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 12 publications found

Genes affected

MYOSLID-AS1 (HGNC:):

LINC01802 (HGNC:52591): (long intergenic non-protein coding RNA 1802)

MIR1302-4 (HGNC:35296): (microRNA 1302-4) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC01802	NR_146973.1	n.316+378T>C		intron_variant	Intron 2 of 2
MIR1302-4	NR_031633.1	n.*4A>G		downstream_gene_variant
MIR1302-4	unassigned_transcript_534	n.*57A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOSLID-AS1	ENST00000412387.5	n.316-28933A>G		intron_variant	Intron 4 of 4	4
MYOSLID-AS1	ENST00000432413.3	n.298-15016A>G		intron_variant	Intron 4 of 5	3
LINC01802	ENST00000438824.2	n.750+378T>C		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36291 AN: 152036 Hom.: 6022 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0943

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.214

GnomAD2 exomes AF: 0.180 AC: 44292 AN: 245688 AF XY: 0.174

Gnomad AFR exome AF: 0.472

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.163

Gnomad FIN exome AF: 0.0891

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.169 AC: 64388 AN: 380156 Hom.: 6310 Cov.: 0 AF XY: 0.168 AC XY: 36337 AN XY: 216576

African (AFR) AF: 0.472 AC: 4914 AN: 10422

American (AMR) AF: 0.227 AC: 8228 AN: 36274

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 1721 AN: 11738

East Asian (EAS) AF: 0.172 AC: 2262 AN: 13166

South Asian (SAS) AF: 0.196 AC: 13071 AN: 66642

European-Finnish (FIN) AF: 0.0961 AC: 3106 AN: 32316

Middle Eastern (MID) AF: 0.162 AC: 199 AN: 1230

European-Non Finnish (NFE) AF: 0.147 AC: 28135 AN: 191840

Other (OTH) AF: 0.167 AC: 2752 AN: 16528

GnomAD4 genome AF: 0.239 AC: 36335 AN: 152154 Hom.: 6030 Cov.: 32 AF XY: 0.235 AC XY: 17464 AN XY: 74380

African (AFR) AF: 0.466 AC: 19308 AN: 41462

American (AMR) AF: 0.196 AC: 2998 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3468

East Asian (EAS) AF: 0.176 AC: 910 AN: 5178

South Asian (SAS) AF: 0.199 AC: 961 AN: 4820

European-Finnish (FIN) AF: 0.0943 AC: 1000 AN: 10610

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10025 AN: 68006

Other (OTH) AF: 0.212 AC: 448 AN: 2114

Alfa AF: 0.197 Hom.: 1984

Bravo AF: 0.258

Asia WGS AF: 0.189 AC: 659 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.014
DANN	Benign	0.27
PhyloP100		-1.9

Splicing

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

Other links and lift over

dbSNP: rs10173558; hg19: chr2-208133995; COSMIC: COSV68660683;