rs4620509

Variant names:

• chr1-66984258-A-G
• rs4620509
• NM_001077700.3:c.1370-314A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001077700.3(MIER1):​c.1370-314A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,162 control chromosomes in the GnomAD database, including 3,966 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 (3966 hom., cov: 33)
• Consequence: MIER1 NM_001077700.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 2 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]

SLC35D1 (HGNC:20800): (solute carrier family 35 member D1) Glycosylation of cellular glycoconjugates occurs in the endoplasmic reticulum (ER) and Golgi compartment, and requires transport of nucleotide sugars from the cytosol into the lumen of the ER and Golgi by specific transporters. The protein encoded by this gene resides in the ER, and transports both UDP-glucuronic acid (UDP-GlcA) and UDP-N-acetylgalactosamine (UDP-GalNAc) from the cytoplasm to the ER lumen. It may participate in glucuronidation and/or chondroitin sulfate biosynthesis. Mutations in this gene are associated with Schneckenbecken dysplasia.[provided by RefSeq, Sep 2009]

SLC35D1 Gene-Disease associations (from GenCC):

• schneckenbecken dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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 rank	MANE	Protein	UniProt
MIER1	NM_001077700.3	c.1370-314A>G		intron_variant	Intron 13 of 13	ENST00000401041.6	NP_001071168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIER1	ENST00000401041.6	c.1370-314A>G		intron_variant	Intron 13 of 13	2	NM_001077700.3	ENSP00000383820.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33112 AN: 152044 Hom.: 3966 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.218 AC: 33114 AN: 152162 Hom.: 3966 Cov.: 33 AF XY: 0.218 AC XY: 16204 AN XY: 74378

African (AFR) AF: 0.163 AC: 6778 AN: 41534

American (AMR) AF: 0.169 AC: 2587 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3470

East Asian (EAS) AF: 0.123 AC: 635 AN: 5182

South Asian (SAS) AF: 0.126 AC: 606 AN: 4818

European-Finnish (FIN) AF: 0.363 AC: 3836 AN: 10574

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17364 AN: 67974

Other (OTH) AF: 0.210 AC: 444 AN: 2110

Alfa AF: 0.225 Hom.: 519

Bravo AF: 0.203

Asia WGS AF: 0.129 AC: 448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.71
PhyloP100		1.1
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: rs4620509; hg19: chr1-67449941;