chr22-49543536-G-A

Variant names:

• chr22-49543536-G-A
• rs135771
• ENST00000414287.6:n.101-102324C>T

Variant summary

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

The ENST00000414287.6(MIR3667HG):​n.101-102324C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 154,486 control chromosomes in the GnomAD database, including 2,484 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 0.16 (2464 hom., cov: 32)
  • Exomes 𝑓: 0.10 (20 hom.)
• Consequence: MIR3667HG ENST00000414287.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 3 publications found

Genes affected

MIR3667HG (HGNC:28010): (MIR3667 host gene)

MIR3667 (HGNC:38990): (microRNA 3667) 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000414287.6. 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
	MIR3667HG	NR_110522.2		n.115+113869C>T		intron	N/A
	MIR3667HG	NR_110523.2		n.116-102324C>T		intron	N/A
	MIR3667	NR_037440.1		n.-70C>T		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR3667HG	ENST00000414287.6	TSL:1	n.101-102324C>T		intron	N/A
	MIR3667HG	ENST00000416411.1	TSL:4	n.54-102324C>T		intron	N/A
	MIR3667HG	ENST00000752354.1		n.116-53284C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24514 AN: 151866 Hom.: 2463 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0569

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.102 AC: 255 AN: 2502 Hom.: 20 AF XY: 0.0997 AC XY: 128 AN XY: 1284

African (AFR) AF: 0.171 AC: 13 AN: 76

American (AMR) AF: 0.00 AC: 0 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.106 AC: 10 AN: 94

European-Finnish (FIN) AF: 0.0545 AC: 17 AN: 312

Middle Eastern (MID) AF: 0.100 AC: 164 AN: 1632

European-Non Finnish (NFE) AF: 0.0924 AC: 17 AN: 184

Other (OTH) AF: 0.177 AC: 34 AN: 192

GnomAD4 genome AF: 0.162 AC: 24546 AN: 151984 Hom.: 2464 Cov.: 32 AF XY: 0.159 AC XY: 11835 AN XY: 74304

African (AFR) AF: 0.272 AC: 11274 AN: 41448

American (AMR) AF: 0.112 AC: 1709 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3466

East Asian (EAS) AF: 0.306 AC: 1558 AN: 5092

South Asian (SAS) AF: 0.114 AC: 549 AN: 4814

European-Finnish (FIN) AF: 0.0569 AC: 603 AN: 10606

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7740 AN: 67948

Other (OTH) AF: 0.153 AC: 323 AN: 2110

Alfa AF: 0.144 Hom.: 2788

Bravo AF: 0.174

Asia WGS AF: 0.208 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.37
DANN	Benign	0.56
PhyloP100		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Other links and lift over

dbSNP: rs135771; hg19: chr22-49937184; COSMIC: COSV69267097;