dbSNP rs10425222: ENSG00000269564:n.438C>A (chr19-53788945-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000597420.2(ENSG00000269564):n.438C>A 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 0.0687 in 299,482 control chromosomes in the GnomAD database, including 1,281 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 0.083 ( 847 hom., cov: 32)

Exomes 𝑓: 0.054 ( 434 hom. )

Consequence

ENSG00000269564
ENST00000597420.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.694

Publications

11 publications found

Variant links:

Genes affected

ENSG00000269564 (HGNC:):

ENSG00000269564 links:

MIR373 (HGNC:31787): (microRNA 373) 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]

MIR373 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect
MIR373	NR_029866.1 link	n.*172C>A	downstream_gene_variant
MIR373	unassigned_transcript_3402	n.*214C>A	downstream_gene_variant
MIR373	unassigned_transcript_3403	n.*175C>A	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000269564	ENST00000597420.2 link	n.438C>A		non_coding_transcript_exon_variant	Exon 2 of 2	6
MIR373	ENST00000362273.1 link	n.*172C>A		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0828

AC:

12567

AN:

151802

Hom.:

847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.0648

Gnomad AMR

AF:

0.0618

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0342

Gnomad OTH

AF:

0.0772

GnomAD4 exome

AF:

0.0541

AC:

7989

AN:

147562

Hom.:

434

Cov.:

AF XY:

0.0608

AC XY:

4969

AN XY:

81704

show subpopulations

African (AFR)

AF:

0.179

AC:

419

AN:

2344

American (AMR)

AF:

0.0434

AC:

242

AN:

5576

Ashkenazi Jewish (ASJ)

AF:

0.0217

AC:

AN:

3000

East Asian (EAS)

AF:

0.101

AC:

362

AN:

3602

South Asian (SAS)

AF:

0.111

AC:

3602

AN:

32488

European-Finnish (FIN)

AF:

0.0147

AC:

170

AN:

11590

Middle Eastern (MID)

AF:

0.0551

AC:

AN:

472

European-Non Finnish (NFE)

AF:

0.0339

AC:

2770

AN:

81762

Other (OTH)

AF:

0.0495

AC:

333

AN:

6728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

341

683

1024

1366

1707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0828

AC:

12576

AN:

151920

Hom.:

847

Cov.:

AF XY:

0.0822

AC XY:

6102

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.184

AC:

7607

AN:

41418

American (AMR)

AF:

0.0616

AC:

938

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3466

East Asian (EAS)

AF:

0.121

AC:

623

AN:

5160

South Asian (SAS)

AF:

0.126

AC:

602

AN:

4790

European-Finnish (FIN)

AF:

0.0174

AC:

184

AN:

10586

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0342

AC:

2326

AN:

67962

Other (OTH)

AF:

0.0797

AC:

168

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

541

1082

1622

2163

2704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0496

Hom.:

Bravo

AF:

0.0897

Asia WGS

AF:

0.186

AC:

648

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.77

(source)

DANN

Benign

0.32

PhyloP100

-0.69

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over