rs731085

Variant names:

• chr22-46112885-C-G
• rs731085
• ENST00000360737.4:n.3517C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-46112885-C-G
• chr22-46112885-C-T

Variant summary

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

The ENST00000360737.4(MIRLET7BHG):​n.3517C>G 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 0.375 in 487,820 control chromosomes in the GnomAD database, including 41,229 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 (20036 hom., cov: 33)
  • Exomes 𝑓: 0.34 (21193 hom.)
• Consequence: MIRLET7BHG ENST00000360737.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359
• Publications: 13 publications found

Genes affected

MIRLET7BHG (HGNC:37189): (MIRLET7B host gene)

LOC124905135 (HGNC:):

MIRLET7A3 (HGNC:31478): (microRNA let-7a-3) 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIRLET7BHG	NR_027033.2	n.3674C>G		non_coding_transcript_exon_variant	Exon 6 of 6
MIRLET7BHG	NR_110479.1	n.3523C>G		non_coding_transcript_exon_variant	Exon 5 of 5
LOC124905135	XM_047441694.1	c.*8296C>G		3_prime_UTR_variant	Exon 2 of 2		XP_047297650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIRLET7BHG	ENST00000360737.4	n.3517C>G		non_coding_transcript_exon_variant	Exon 5 of 5	2
MIRLET7BHG	ENST00000794300.1	n.745C>G		non_coding_transcript_exon_variant	Exon 6 of 6
MIRLET7BHG	ENST00000794301.1	n.626C>G		non_coding_transcript_exon_variant	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69887 AN: 152000 Hom.: 19995 Cov.: 33

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.336 AC: 112743 AN: 335702 Hom.: 21193 Cov.: 0 AF XY: 0.332 AC XY: 62427 AN XY: 188036

African (AFR) AF: 0.817 AC: 7930 AN: 9702

American (AMR) AF: 0.256 AC: 8399 AN: 32808

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 3205 AN: 9936

East Asian (EAS) AF: 0.00180 AC: 22 AN: 12202

South Asian (SAS) AF: 0.303 AC: 18912 AN: 62336

European-Finnish (FIN) AF: 0.362 AC: 10397 AN: 28740

Middle Eastern (MID) AF: 0.368 AC: 696 AN: 1890

European-Non Finnish (NFE) AF: 0.355 AC: 58067 AN: 163400

Other (OTH) AF: 0.348 AC: 5115 AN: 14688

GnomAD4 genome AF: 0.460 AC: 69970 AN: 152118 Hom.: 20036 Cov.: 33 AF XY: 0.453 AC XY: 33703 AN XY: 74356

African (AFR) AF: 0.803 AC: 33326 AN: 41512

American (AMR) AF: 0.324 AC: 4945 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1106 AN: 3470

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5180

South Asian (SAS) AF: 0.301 AC: 1452 AN: 4828

European-Finnish (FIN) AF: 0.361 AC: 3811 AN: 10566

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23961 AN: 67974

Other (OTH) AF: 0.401 AC: 847 AN: 2112

Alfa AF: 0.284 Hom.: 775

Bravo AF: 0.471

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.44
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs731085; hg19: chr22-46508765; COSMIC: COSV62450728;