rs1542848

Positions:

• chr3-12576497-G-A
• chr3-12576497-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MKRN2	NM_014160.5	c.858-134G>A		intron_variant		ENST00000170447.12	NP_054879.3
MKRN2	NM_001271707.2	c.729-134G>A		intron_variant			NP_001258636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKRN2	ENST00000170447.12	c.858-134G>A		intron_variant		1	NM_014160.5	ENSP00000170447	P1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58477 AN: 151764 Hom.: 11895 Cov.: 30

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

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.369

Gnomad4 EAS exome AF: 0.0947

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.385 AC: 58514 AN: 151882 Hom.: 11907 Cov.: 30 AF XY: 0.378 AC XY: 28026 AN XY: 74226

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.0819

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.383

Alfa AF: 0.348 Hom.: 2987

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
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs1542848; hg19: chr3-12617996;