rs11706408

chr3-12545634-A-Gchr3-12545634-A-T

Variant summary

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

The NM_001378007.1(MKRN2OS):c.-89-3612T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 480,938 control chromosomes in the GnomAD database, including 1,477 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 0.075 (485 hom., cov: 32)
  • Exomes 𝑓: 0.075 (992 hom.)
• Consequence: MKRN2OS NM_001378007.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

Genes affected

MKRN2OS (HGNC:40375): (MKRN2 opposite strand)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MKRN2OS	NM_001378007.1	c.-89-3612T>C		intron_variant
MKRN2OS	NM_001378008.1	c.-70-3631T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MKRN2OS	ENST00000567514.1	n.304-2405T>C		intron_variant, non_coding_transcript_variant		5
MKRN2OS	ENST00000678164.1	n.1068-3612T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11450 AN: 152162 Hom.: 487 Cov.: 32

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0579

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.0817

GnomAD4 exome AF: 0.0751 AC: 24690 AN: 328658 Hom.: 992 AF XY: 0.0737 AC XY: 12558 AN XY: 170310

Gnomad4 AFR exome AF: 0.0815

Gnomad4 AMR exome AF: 0.0571

Gnomad4 ASJ exome AF: 0.0984

Gnomad4 EAS exome AF: 0.000121

Gnomad4 SAS exome AF: 0.0308

Gnomad4 FIN exome AF: 0.0700

Gnomad4 NFE exome AF: 0.0881

Gnomad4 OTH exome AF: 0.0788

GnomAD4 genome AF: 0.0752 AC: 11452 AN: 152280 Hom.: 485 Cov.: 32 AF XY: 0.0716 AC XY: 5330 AN XY: 74472

Gnomad4 AFR AF: 0.0770

Gnomad4 AMR AF: 0.0633

Gnomad4 ASJ AF: 0.0968

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.0579

Gnomad4 NFE AF: 0.0884

Gnomad4 OTH AF: 0.0809

Alfa AF: 0.0767 Hom.: 520

Bravo AF: 0.0747

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.6
Dann	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11706408; hg19: chr3-12587133;