rs4553158

Variant names:

• chr1-66970763-A-G
• rs4553158
• NM_001077700.3:c.773-45A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-66970763-A-G
• chr1-66970763-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077700.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIER1	NM_001077700.3	MANE Select	c.773-45A>G		intron	N/A	NP_001071168.2	Q8N108-12
	MIER1	NM_001350530.2		c.884-45A>G		intron	N/A	NP_001337459.1
	MIER1	NM_001146110.2		c.665-45A>G		intron	N/A	NP_001139582.1	Q8N108-13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIER1	ENST00000401041.6	TSL:2 MANE Select	c.773-45A>G		intron	N/A	ENSP00000383820.1	Q8N108-12
	MIER1	ENST00000357692.6	TSL:1	c.665-45A>G		intron	N/A	ENSP00000350321.2	Q8N108-13
	MIER1	ENST00000355356.3	TSL:1	c.614-45A>G		intron	N/A	ENSP00000347514.3	Q8N108-11

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

GnomAD2 exomes AF: 0.144 AC: 22602 AN: 157038 AF XY: 0.147

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 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

African (AFR) AF: 0.0267 AC: 696 AN: 26110

American (AMR) AF: 0.0740 AC: 1751 AN: 23668

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2168 AN: 19538

East Asian (EAS) AF: 0.0640 AC: 2252 AN: 35164

South Asian (SAS) AF: 0.0921 AC: 5589 AN: 60716

European-Finnish (FIN) AF: 0.241 AC: 12029 AN: 49882

Middle Eastern (MID) AF: 0.0945 AC: 473 AN: 5006

European-Non Finnish (NFE) AF: 0.174 AC: 168568 AN: 969414

Other (OTH) AF: 0.153 AC: 7969 AN: 51920

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

African (AFR) AF: 0.0337 AC: 1400 AN: 41568

American (AMR) AF: 0.0958 AC: 1465 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3470

East Asian (EAS) AF: 0.0794 AC: 412 AN: 5190

South Asian (SAS) AF: 0.0923 AC: 446 AN: 4830

European-Finnish (FIN) AF: 0.236 AC: 2493 AN: 10582

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11465 AN: 67918

Other (OTH) AF: 0.133 AC: 281 AN: 2112

Alfa AF: 0.148 Hom.: 5567

Bravo AF: 0.107

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.11
DANN	Benign	0.34
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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