X-154379351-A-G

Variant names:

• chrX-154379351-A-G
• rs111878670
• NM_000117.3:c.-134A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000117.3(EMD):​c.-134A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 638,444 control chromosomes in the GnomAD database, including 6 homozygotes. There are 210 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (5 hom., 160 hem., cov: 26)
  • Exomes 𝑓: 0.00036 (1 hom. 50 hem.)
• Consequence: EMD NM_000117.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.666
• Publications: 0 publications found

Genes affected

EMD (HGNC:3331): (emerin) Emerin is a serine-rich nuclear membrane protein and a member of the nuclear lamina-associated protein family. It mediates membrane anchorage to the cytoskeleton. Dreifuss-Emery muscular dystrophy is an X-linked inherited degenerative myopathy resulting from mutation in the emerin gene. [provided by RefSeq, Jul 2008]

EMD Gene-Disease associations (from GenCC):

• X-linked Emery-Dreifuss muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• heart conduction disease

  Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-154379351-A-G is Benign according to our data. Variant chrX-154379351-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1209222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00513 (581/113324) while in subpopulation AFR AF = 0.018 (564/31331). AF 95% confidence interval is 0.0168. There are 5 homozygotes in GnomAd4. There are 160 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMD	NM_000117.3	c.-134A>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000369842.9	NP_000108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMD	ENST00000369842.9	c.-134A>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_000117.3	ENSP00000358857.4

Frequencies

GnomAD3 genomes AF: 0.00514 AC: 582 AN: 113275 Hom.: 5 Cov.: 26

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000732

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000350

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000751

Gnomad OTH AF: 0.00328

GnomAD4 exome AF: 0.000364 AC: 191 AN: 525120 Hom.: 1 Cov.: 8 AF XY: 0.000341 AC XY: 50 AN XY: 146744

African (AFR) AF: 0.0150 AC: 170 AN: 11316

American (AMR) AF: 0.000371 AC: 6 AN: 16187

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11429

East Asian (EAS) AF: 0.00 AC: 0 AN: 21647

South Asian (SAS) AF: 0.0000316 AC: 1 AN: 31660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27430

Middle Eastern (MID) AF: 0.000554 AC: 1 AN: 1806

European-Non Finnish (NFE) AF: 0.00000265 AC: 1 AN: 377613

Other (OTH) AF: 0.000461 AC: 12 AN: 26032

GnomAD4 genome AF: 0.00513 AC: 581 AN: 113324 Hom.: 5 Cov.: 26 AF XY: 0.00450 AC XY: 160 AN XY: 35556

African (AFR) AF: 0.0180 AC: 564 AN: 31331

American (AMR) AF: 0.000640 AC: 7 AN: 10944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2658

East Asian (EAS) AF: 0.00 AC: 0 AN: 3551

South Asian (SAS) AF: 0.000351 AC: 1 AN: 2848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 211

European-Non Finnish (NFE) AF: 0.0000752 AC: 4 AN: 53223

Other (OTH) AF: 0.00323 AC: 5 AN: 1546

Alfa AF: 0.00377 Hom.: 10

Bravo AF: 0.00543

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.46
PhyloP100		0.67
PromoterAI		-0.078	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs111878670; hg19: chrX-153607711;