rs7256241

Variant names:

• chr19-53708649-T-G
• rs7256241
• ENST00000710708.1:n.463-4330T>G

Variant summary

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

The ENST00000710708.1(ENSG00000269842):​n.463-4330T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 486,520 control chromosomes in the GnomAD database, including 53,291 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 0.46 (16233 hom., cov: 32)
  • Exomes 𝑓: 0.47 (37058 hom.)
• Consequence: ENSG00000269842 ENST00000710708.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 11 publications found

Genes affected

ENSG00000269842 (HGNC:):

MIR518C (HGNC:32109): (microRNA 518c) 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR518C	NR_030199.1	n.-86T>G		upstream_gene_variant
MIR518C	unassigned_transcript_3352	n.-109T>G		upstream_gene_variant
MIR518C	unassigned_transcript_3353	n.-147T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000269842	ENST00000710708.1	n.463-4330T>G		intron_variant	Intron 3 of 9
MIR518C	ENST00000384822.3	n.-86T>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70033 AN: 151838 Hom.: 16209 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.467 AC: 156151 AN: 334564 Hom.: 37058 AF XY: 0.470 AC XY: 88916 AN XY: 189026

African (AFR) AF: 0.474 AC: 3998 AN: 8436

American (AMR) AF: 0.523 AC: 14438 AN: 27580

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 3507 AN: 10296

East Asian (EAS) AF: 0.428 AC: 5207 AN: 12166

South Asian (SAS) AF: 0.526 AC: 31453 AN: 59830

European-Finnish (FIN) AF: 0.498 AC: 15534 AN: 31216

Middle Eastern (MID) AF: 0.476 AC: 1271 AN: 2670

European-Non Finnish (NFE) AF: 0.442 AC: 74115 AN: 167760

Other (OTH) AF: 0.454 AC: 6628 AN: 14610

GnomAD4 genome AF: 0.461 AC: 70117 AN: 151956 Hom.: 16233 Cov.: 32 AF XY: 0.466 AC XY: 34640 AN XY: 74270

African (AFR) AF: 0.480 AC: 19897 AN: 41432

American (AMR) AF: 0.505 AC: 7709 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1219 AN: 3468

East Asian (EAS) AF: 0.441 AC: 2272 AN: 5154

South Asian (SAS) AF: 0.538 AC: 2594 AN: 4818

European-Finnish (FIN) AF: 0.501 AC: 5295 AN: 10560

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29854 AN: 67956

Other (OTH) AF: 0.441 AC: 931 AN: 2110

Alfa AF: 0.442 Hom.: 38003

Bravo AF: 0.456

Asia WGS AF: 0.537 AC: 1865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.16
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs7256241; hg19: chr19-54211903; COSMIC: COSV66010675;