chr6-10439735-T-C

Variant names:

• chr6-10439735-T-C
• rs9295535
• ENST00000581998.1:n.19T>C

Variant summary

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

The ENST00000581998.1(MIR5689):​n.19T>C 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 0.2 in 147,136 control chromosomes in the GnomAD database, including 3,085 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 0.20 (3082 hom., cov: 23)
  • Exomes 𝑓: 0.20 (3 hom.)
• Consequence: MIR5689 ENST00000581998.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 12 publications found

Genes affected

MIR5689 (HGNC:43479): (microRNA 5689) 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]

TFAP2A-AS1 (HGNC:40579): (TFAP2A antisense RNA 1)

LINC00518 (HGNC:28626): (long intergenic non-protein coding RNA 518)

MIR5689HG (HGNC:52007): (MIR5689 host gene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000581998.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR5689	NR_049872.1		n.19T>C		non_coding_transcript_exon	Exon 1 of 1
	MIR5689HG	NR_132993.1		n.76+5331T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR5689	ENST00000581998.1	TSL:6	n.19T>C		non_coding_transcript_exon	Exon 1 of 1
	TFAP2A-AS1	ENST00000366312.2	TSL:3	n.76+5331T>C		intron	N/A
	TFAP2A-AS1	ENST00000449333.2	TSL:3	n.862+5331T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.200 AC: 29338 AN: 146954 Hom.: 3085 Cov.: 23

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.219

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.201

GnomAD2 exomes AF: 0.300 AC: 3 AN: 10 AF XY: 0.500

Gnomad NFE exome AF: 0.300

GnomAD4 exome AF: 0.200 AC: 12 AN: 60 Hom.: 3 Cov.: 0 AF XY: 0.250 AC XY: 6 AN XY: 24

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.212 AC: 11 AN: 52

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.200 AC: 29345 AN: 147076 Hom.: 3082 Cov.: 23 AF XY: 0.201 AC XY: 14397 AN XY: 71766

African (AFR) AF: 0.148 AC: 5979 AN: 40330

American (AMR) AF: 0.211 AC: 3154 AN: 14952

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 749 AN: 3408

East Asian (EAS) AF: 0.287 AC: 1354 AN: 4724

South Asian (SAS) AF: 0.347 AC: 1552 AN: 4476

European-Finnish (FIN) AF: 0.168 AC: 1675 AN: 9944

Middle Eastern (MID) AF: 0.201 AC: 58 AN: 288

European-Non Finnish (NFE) AF: 0.217 AC: 14297 AN: 66020

Other (OTH) AF: 0.199 AC: 408 AN: 2046

Alfa AF: 0.219 Hom.: 1708

Bravo AF: 0.199

Asia WGS AF: 0.282 AC: 981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.70
PhyloP100		0.45

Splicing

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

Other links and lift over

dbSNP: rs9295535; hg19: chr6-10439968;