Genetic Variant XM_047441694.1:c.*8296C>G (chr22-46112885-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_047441694.1(LOC124905135):c.*8296C>G variant causes a 3 prime UTR 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

LOC124905135
XM_047441694.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.359

Variant links:

Genes affected

LOC124905135 (HGNC:):

LOC124905135 links:

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

MIRLET7BHG links:

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]

MIRLET7A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	Exon rank	Protein
LOC124905135	XM_047441694.1 link	c.*8296C>G	3_prime_UTR_variant	Exon 2 of 2	XP_047297650.1
LOC124905135	XM_047441695.1 link	c.*8296C>G	3_prime_UTR_variant	Exon 2 of 2	XP_047297651.1
LOC124905135	XM_047441696.1 link	c.*8296C>G	3_prime_UTR_variant	Exon 2 of 2	XP_047297652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIRLET7BHG	ENST00000360737.4 link	n.3517C>G		non_coding_transcript_exon_variant	Exon 5 of 5	2
MIRLET7A3	ENST00000362116.3 link	n.*63C>G		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.460

AC:

69887

AN:

152000

Hom.:

19995

Cov.:

show subpopulations

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.:

AF XY:

0.332

AC XY:

62427

AN XY:

188036

show subpopulations

Gnomad4 AFR exome

AF:

0.817

Gnomad4 AMR exome

AF:

0.256

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.00180

Gnomad4 SAS exome

AF:

0.303

Gnomad4 FIN exome

AF:

0.362

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.348

GnomAD4 genome

AF:

0.460

AC:

69970

AN:

152118

Hom.:

20036

Cov.:

AF XY:

0.453

AC XY:

33703

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.803

Gnomad4 AMR

AF:

0.324

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.301

Gnomad4 FIN

AF:

0.361

Gnomad4 NFE

AF:

0.353

Gnomad4 OTH

AF:

0.401

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over