rs744893

Variant names:

• chr6-158781208-G-C
• rs744893
• NM_001111077.2:c.698+2312C>G

Variant summary

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

The NM_001111077.2(EZR):​c.698+2312C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,130 control chromosomes in the GnomAD database, including 3,031 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 0.19 (3031 hom., cov: 32)
• Consequence: EZR NM_001111077.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 7 publications found

Genes affected

EZR (HGNC:12691): (ezrin) The cytoplasmic peripheral membrane protein encoded by this gene functions as a protein-tyrosine kinase substrate in microvilli. As a member of the ERM protein family, this protein serves as an intermediate between the plasma membrane and the actin cytoskeleton. This protein plays a key role in cell surface structure adhesion, migration and organization, and it has been implicated in various human cancers. A pseudogene located on chromosome 3 has been identified for this gene. Alternatively spliced variants have also been described for this gene. [provided by RefSeq, Jul 2008]

EZR Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EZR	NM_001111077.2	c.698+2312C>G		intron_variant	Intron 7 of 13	ENST00000367075.4	NP_001104547.1
EZR	NM_003379.5	c.698+2312C>G		intron_variant	Intron 6 of 12		NP_003370.2
EZR	XM_011536110.2	c.290+2312C>G		intron_variant	Intron 3 of 9		XP_011534412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EZR	ENST00000367075.4	c.698+2312C>G		intron_variant	Intron 7 of 13	1	NM_001111077.2	ENSP00000356042.3
EZR	ENST00000337147.11	c.698+2312C>G		intron_variant	Intron 6 of 12	1		ENSP00000338934.7

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28463 AN: 152012 Hom.: 3030 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.187 AC: 28477 AN: 152130 Hom.: 3031 Cov.: 32 AF XY: 0.188 AC XY: 13961 AN XY: 74372

African (AFR) AF: 0.108 AC: 4485 AN: 41502

American (AMR) AF: 0.132 AC: 2017 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3470

East Asian (EAS) AF: 0.0535 AC: 277 AN: 5182

South Asian (SAS) AF: 0.275 AC: 1325 AN: 4816

European-Finnish (FIN) AF: 0.262 AC: 2765 AN: 10568

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

European-Non Finnish (NFE) AF: 0.240 AC: 16292 AN: 67992

Other (OTH) AF: 0.175 AC: 369 AN: 2114

Alfa AF: 0.212 Hom.: 448

Bravo AF: 0.167

Asia WGS AF: 0.173 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.78
PhyloP100		-0.066
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs744893; hg19: chr6-159202240;