Genetic Variant MIR646HG:n.451G>A (chr20-60070672-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000625080.1(MIR646HG):n.451G>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 0.000155 in 1,367,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

MIR646HG
ENST00000625080.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.786

Publications

2 publications found

Variant links:

Genes affected

MIR646HG (HGNC:27659): (MIR646 host gene)

MIR646HG links:

LINC02910 (HGNC:26601): (long intergenic non-protein coding RNA 2910)

LINC02910 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LINC02910	NR_161291.1 link	n.451G>A	non_coding_transcript_exon_variant	Exon 4 of 4
LINC02910	NR_161292.1 link	n.371G>A	non_coding_transcript_exon_variant	Exon 3 of 3
LINC02910	NR_161293.1 link	n.376-316G>A	intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MIR646HG	ENST00000625080.1 link	n.451G>A	non_coding_transcript_exon_variant	Exon 4 of 4	2
MIR646HG	ENST00000660831.1 link	n.443G>A	non_coding_transcript_exon_variant	Exon 3 of 3
MIR646HG	ENST00000715828.1 link	n.82+14664G>A	intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.000789

AC:

120

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00277

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000159

AC:

AN:

251434

AF XY:

0.000132

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000749

AC:

AN:

1215578

Hom.:

Cov.:

AF XY:

0.0000664

AC XY:

AN XY:

602448

show subpopulations

African (AFR)

AF:

0.00300

AC:

AN:

26300

American (AMR)

AF:

0.0000536

AC:

AN:

37290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16896

East Asian (EAS)

AF:

0.00

AC:

AN:

16806

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32596

Middle Eastern (MID)

AF:

0.000224

AC:

AN:

4474

European-Non Finnish (NFE)

AF:

0.00000524

AC:

AN:

953964

Other (OTH)

AF:

0.0000681

AC:

AN:

44026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000795

AC:

121

AN:

152284

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00279

AC:

116

AN:

41566

American (AMR)

AF:

0.000131

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000888

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 26, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.22

(source)

DANN

Benign

0.27

PhyloP100

-0.79

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr20-60070672-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over