rs201140396

Variant names:

• chrX-154379677-C-G
• rs201140396
• NM_000117.3:c.83-13C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-154379677-C-G
• chrX-154379677-C-T
• chrX-154379677-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000117.3(EMD):​c.83-13C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000555 in 1,205,852 control chromosomes in the GnomAD database, including 3 homozygotes. There are 180 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., 83 hem., cov: 25)
  • Exomes 𝑓: 0.00032 (2 hom. 97 hem.)
• Consequence: EMD NM_000117.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.467
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• heart conduction disease

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-154379677-C-G is Benign according to our data. Variant chrX-154379677-C-G is described in ClinVar as Benign. ClinVar VariationId is 42279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00282 (318/112686) while in subpopulation AFR AF = 0.00969 (302/31155). AF 95% confidence interval is 0.00879. There are 1 homozygotes in GnomAd4. There are 83 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 83 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000117.3. 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
	EMD	NM_000117.3	MANE Select	c.83-13C>G		intron	N/A	NP_000108.1	P50402

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMD	ENST00000369842.9	TSL:1 MANE Select	c.83-13C>G		intron	N/A	ENSP00000358857.4	P50402
	EMD	ENST00000933532.1		c.83-13C>G		intron	N/A	ENSP00000603591.1
	EMD	ENST00000933533.1		c.83-13C>G		intron	N/A	ENSP00000603592.1

Frequencies

GnomAD3 genomes AF: 0.00281 AC: 316 AN: 112638 Hom.: 1 Cov.: 25

Gnomad AFR AF: 0.00965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000927

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00108

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000377

Gnomad OTH AF: 0.000663

GnomAD2 exomes AF: 0.000755 AC: 129 AN: 170813 AF XY: 0.000428

Gnomad AFR exome AF: 0.00999

Gnomad AMR exome AF: 0.000482

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000135

Gnomad OTH exome AF: 0.000473

GnomAD4 exome AF: 0.000321 AC: 351 AN: 1093166 Hom.: 2 Cov.: 31 AF XY: 0.000270 AC XY: 97 AN XY: 359708

African (AFR) AF: 0.0103 AC: 271 AN: 26311

American (AMR) AF: 0.000484 AC: 17 AN: 35094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19330

East Asian (EAS) AF: 0.0000332 AC: 1 AN: 30145

South Asian (SAS) AF: 0.0000926 AC: 5 AN: 53970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39263

Middle Eastern (MID) AF: 0.000732 AC: 3 AN: 4098

European-Non Finnish (NFE) AF: 0.00000596 AC: 5 AN: 839044

Other (OTH) AF: 0.00107 AC: 49 AN: 45911

GnomAD4 genome AF: 0.00282 AC: 318 AN: 112686 Hom.: 1 Cov.: 25 AF XY: 0.00238 AC XY: 83 AN XY: 34858

African (AFR) AF: 0.00969 AC: 302 AN: 31155

American (AMR) AF: 0.000925 AC: 10 AN: 10805

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.00108 AC: 3 AN: 2776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6219

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000377 AC: 2 AN: 53109

Other (OTH) AF: 0.000655 AC: 1 AN: 1526

Alfa AF: 0.000174 Hom.: 1

Bravo AF: 0.00302

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Emery-Dreifuss muscular dystrophy 1, X-linked (1)
-	-	1	not provided (1)
-	-	1	X-linked Emery-Dreifuss muscular dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.40
PhyloP100		-0.47
PromoterAI		-0.058	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs201140396; hg19: chrX-153608037;