rs7726354

Positions:

• chr5-56960656-C-T

Variant summary

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

The ENST00000440000.5(MIER3):​c.-104-1136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 152,294 control chromosomes in the GnomAD database, including 176 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 0.046 (176 hom., cov: 32)
• Consequence: MIER3 ENST00000440000.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

Genes affected

MIER3 (HGNC:26678): (MIER family member 3) Predicted to enable histone deacetylase binding activity and transcription corepressor activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIER3	ENST00000440000.5	c.-104-1136G>A		intron_variant		5
MIER3	ENST00000497185.2	n.44-10004G>A		intron_variant, non_coding_transcript_variant		5
MIER3	ENST00000546593.5	n.44-1136G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6937 AN: 152176 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0456 AC: 6937 AN: 152294 Hom.: 176 Cov.: 32 AF XY: 0.0450 AC XY: 3350 AN XY: 74462

Gnomad4 AFR AF: 0.0293

Gnomad4 AMR AF: 0.0520

Gnomad4 ASJ AF: 0.0631

Gnomad4 EAS AF: 0.0608

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.0378

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0518 Hom.: 110

Bravo AF: 0.0478

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7726354; hg19: chr5-56256483;