rs6841938

Positions:

• chr4-36426426-G-A

Variant summary

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

The NR_031701.1(MIR1255B1):​n.3C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 155,446 control chromosomes in the GnomAD database, including 988 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 0.10 (970 hom., cov: 33)
  • Exomes 𝑓: 0.093 (18 hom.)
• Consequence: MIR1255B1 NR_031701.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

Genes affected

MIR1255B1 (HGNC:35366): (microRNA 1255b-1) 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR1255B1	NR_031701.1	n.3C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR1255B1	ENST00000636325.1	n.3C>T		mature_miRNA_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15578 AN: 152036 Hom.: 969 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0959

GnomAD3 exomes AF: 0.0863 AC: 550 AN: 6372 Hom.: 24 AF XY: 0.0796 AC XY: 246 AN XY: 3090

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.0806

Gnomad ASJ exome AF: 0.0663

Gnomad EAS exome AF: 0.0143

Gnomad SAS exome AF: 0.00909

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.0856

Gnomad OTH exome AF: 0.0676

GnomAD4 exome AF: 0.0933 AC: 307 AN: 3292 Hom.: 18 Cov.: 0 AF XY: 0.0937 AC XY: 175 AN XY: 1868

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.0357

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0242

Gnomad4 FIN exome AF: 0.0943

Gnomad4 NFE exome AF: 0.0858

Gnomad4 OTH exome AF: 0.0856

GnomAD4 genome AF: 0.102 AC: 15591 AN: 152154 Hom.: 970 Cov.: 33 AF XY: 0.0999 AC XY: 7436 AN XY: 74404

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0732

Gnomad4 ASJ AF: 0.0688

Gnomad4 EAS AF: 0.0121

Gnomad4 SAS AF: 0.0276

Gnomad4 FIN AF: 0.0937

Gnomad4 NFE AF: 0.0857

Gnomad4 OTH AF: 0.0949

Alfa AF: 0.0980 Hom.: 98

Bravo AF: 0.105

Asia WGS AF: 0.0340 AC: 118 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	4.1
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6841938; hg19: chr4-36428048;