rs4553158

Positions:

• chr1-66970763-A-G

Variant summary

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

The NM_001077700.3(MIER1):​c.773-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,393,584 control chromosomes in the GnomAD database, including 18,907 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 0.12 (1471 hom., cov: 32)
  • Exomes 𝑓: 0.16 (17436 hom.)
• Consequence: MIER1 NM_001077700.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62

Genes affected

MIER1 (HGNC:29657): (MIER1 transcriptional regulator) This gene encodes a protein that was first identified in Xenopus laevis by its role in a mesoderm induction early response (MIER). The encoded protein functions as a transcriptional regulator. Alternatively spliced transcript variants encode multiple isoforms, some of which lack a C-terminal nuclear localization signal. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIER1	NM_001077700.3	c.773-45A>G		intron_variant		ENST00000401041.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIER1	ENST00000401041.6	c.773-45A>G		intron_variant		2	NM_001077700.3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18481 AN: 152048 Hom.: 1474 Cov.: 32

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0960

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0802

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.132

GnomAD3 exomes AF: 0.144 AC: 22602 AN: 157038 Hom.: 1920 AF XY: 0.147 AC XY: 12525 AN XY: 85288

Gnomad AFR exome AF: 0.0309

Gnomad AMR exome AF: 0.0648

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.0878

Gnomad SAS exome AF: 0.0925

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.162 AC: 201495 AN: 1241418 Hom.: 17436 Cov.: 17 AF XY: 0.161 AC XY: 98901 AN XY: 615156

Gnomad4 AFR exome AF: 0.0267

Gnomad4 AMR exome AF: 0.0740

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.0640

Gnomad4 SAS exome AF: 0.0921

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.121 AC: 18474 AN: 152166 Hom.: 1471 Cov.: 32 AF XY: 0.122 AC XY: 9094 AN XY: 74408

Gnomad4 AFR AF: 0.0337

Gnomad4 AMR AF: 0.0958

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0794

Gnomad4 SAS AF: 0.0923

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.133

Alfa AF: 0.156 Hom.: 3826

Bravo AF: 0.107

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.11
DANN	Benign	0.34

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: rs4553158; hg19: chr1-67436446; COSMIC: COSV62530920;