rs201317128

Variant names:

• chr6-158771237-C-G
• rs201317128
• NM_001111077.2:c.959+7G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-158771237-C-G
• chr6-158771237-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001111077.2(EZR):​c.959+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,455,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: EZR NM_001111077.2 splice_region, intron
• Scores: Splicing: ADA: 0.00007399
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EZR	NM_001111077.2	c.959+7G>C		splice_region_variant, intron_variant	Intron 9 of 13	ENST00000367075.4	NP_001104547.1
EZR	NM_003379.5	c.959+7G>C		splice_region_variant, intron_variant	Intron 8 of 12		NP_003370.2
EZR	XM_011536110.2	c.551+7G>C		splice_region_variant, intron_variant	Intron 5 of 9		XP_011534412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EZR	ENST00000367075.4	c.959+7G>C		splice_region_variant, intron_variant	Intron 9 of 13	1	NM_001111077.2	ENSP00000356042.3
EZR	ENST00000337147.11	c.959+7G>C		splice_region_variant, intron_variant	Intron 8 of 12	1		ENSP00000338934.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 243934 AF XY: 0.00000759

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000912

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1455362 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 723606

African (AFR) AF: 0.00 AC: 0 AN: 33330

American (AMR) AF: 0.00 AC: 0 AN: 43974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25632

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 85012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5606

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1108856

Other (OTH) AF: 0.00 AC: 0 AN: 60096

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.30
DANN	Benign	0.51
PhyloP100		-1.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000074
dbscSNV1_RF	Benign	0.0060
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: rs201317128; hg19: chr6-159192269;