dbSNP rs1542848: MKRN2:c.858-134G>A (chr3-12576497-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014160.5(MKRN2):c.858-134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 579,740 control chromosomes in the GnomAD database, including 38,895 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 0.39 ( 11907 hom., cov: 30)

Exomes 𝑓: 0.34 ( 26988 hom. )

Consequence

MKRN2
NM_014160.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.371

Publications

7 publications found

Variant links:

Genes affected

MKRN2 (HGNC:7113): (makorin ring finger protein 2) This gene encodes a probable E3 ubiquitin ligase containing several zinc finger domains, that is a member of the makorin RING zinc-finger protein family. This gene overlaps the v-raf-1 murine leukemia viral oncogene homolog 1 (RAF1) gene in an antisense orientation and may have a co-regulatory function with RAF1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

MKRN2 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKRN2	NM_014160.5 link	c.858-134G>A		intron_variant	Intron 5 of 7	ENST00000170447.12	NP_054879.3
MKRN2	NM_001271707.2 link	c.729-134G>A		intron_variant	Intron 4 of 6		NP_001258636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKRN2	ENST00000170447.12 link	c.858-134G>A		intron_variant	Intron 5 of 7	1	NM_014160.5	ENSP00000170447.7		Q9H000-1

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58477

AN:

151764

Hom.:

11895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.303

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.0822

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.384

Gnomad OTH

AF:

0.387

GnomAD4 exome

AF:

0.338

AC:

144766

AN:

427858

Hom.:

26988

AF XY:

0.329

AC XY:

74480

AN XY:

226572

show subpopulations

African (AFR)

AF:

0.486

AC:

5132

AN:

10564

American (AMR)

AF:

0.256

AC:

4331

AN:

16912

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

4304

AN:

11678

East Asian (EAS)

AF:

0.0947

AC:

2509

AN:

26506

South Asian (SAS)

AF:

0.167

AC:

6930

AN:

41538

European-Finnish (FIN)

AF:

0.376

AC:

14458

AN:

38422

Middle Eastern (MID)

AF:

0.327

AC:

1078

AN:

3294

European-Non Finnish (NFE)

AF:

0.382

AC:

97772

AN:

255770

Other (OTH)

AF:

0.356

AC:

8252

AN:

23174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

4265

8530

12795

17060

21325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.385

AC:

58514

AN:

151882

Hom.:

11907

Cov.:

AF XY:

0.378

AC XY:

28026

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.488

AC:

20176

AN:

41380

American (AMR)

AF:

0.302

AC:

4608

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

1253

AN:

3468

East Asian (EAS)

AF:

0.0819

AC:

424

AN:

5180

South Asian (SAS)

AF:

0.159

AC:

767

AN:

4814

European-Finnish (FIN)

AF:

0.381

AC:

4006

AN:

10528

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.384

AC:

26092

AN:

67960

Other (OTH)

AF:

0.383

AC:

809

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1757

3514

5270

7027

8784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.357

Hom.:

3858

Bravo

AF:

0.384

Asia WGS

AF:

0.158

AC:

555

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.4

(source)

DANN

Benign

0.78

PhyloP100

-0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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