rs12131222

chr1-66972852-A-T

Variant summary

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

The NM_001077700.3(MIER1):c.1007-45A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 982,136 control chromosomes in the GnomAD database, including 29,295 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 0.22 (3958 hom., cov: 31)
  • Exomes 𝑓: 0.24 (25337 hom.)
• Consequence: MIER1 NM_001077700.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIER1	NM_001077700.3	c.1007-45A>T		intron_variant		ENST00000401041.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIER1	ENST00000401041.6	c.1007-45A>T		intron_variant		2	NM_001077700.3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33112 AN: 151874 Hom.: 3958 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.214

GnomAD3 exomes AF: 0.220 AC: 45046 AN: 204366 Hom.: 5421 AF XY: 0.220 AC XY: 24650 AN XY: 111794

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.125

Gnomad SAS exome AF: 0.134

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.256

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.239 AC: 198349 AN: 830144 Hom.: 25337 Cov.: 11 AF XY: 0.236 AC XY: 102632 AN XY: 435590

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.0924

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.358

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.218 AC: 33116 AN: 151992 Hom.: 3958 Cov.: 31 AF XY: 0.218 AC XY: 16209 AN XY: 74294

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.212

Alfa AF: 0.218 Hom.: 718

Bravo AF: 0.204

Asia WGS AF: 0.130 AC: 452 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	7.6
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12131222; hg19: chr1-67438535; COSMIC: COSV62530780;