chr5-56960656-C-T

Variant names:

• chr5-56960656-C-T
• rs7726354
• ENST00000440000.5:c.-104-1136G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIER3	ENST00000440000.5	c.-104-1136G>A		intron_variant	Intron 1 of 2	5		ENSP00000407169.1
MIER3	ENST00000497185.2	n.44-10004G>A		intron_variant	Intron 1 of 2	5
MIER3	ENST00000546593.5	n.44-1136G>A		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.0293 AC: 1219 AN: 41560

American (AMR) AF: 0.0520 AC: 796 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 219 AN: 3472

East Asian (EAS) AF: 0.0608 AC: 315 AN: 5182

South Asian (SAS) AF: 0.0344 AC: 166 AN: 4828

European-Finnish (FIN) AF: 0.0378 AC: 401 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0542 AC: 3685 AN: 68022

Other (OTH) AF: 0.0497 AC: 105 AN: 2112

Alfa AF: 0.0521 Hom.: 479

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
PhyloP100		0.057

Splicing

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

Other links and lift over

dbSNP: rs7726354; hg19: chr5-56256483;