rs1028360

Variant names:

• chrX-32485110-G-C
• rs1028360
• NM_004006.3:c.2623-11C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-32485110-G-C
• chrX-32485110-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004006.3(DMD):​c.2623-11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,202,199 control chromosomes in the GnomAD database, including 157 homozygotes. There are 1,503 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (81 hom., 678 hem., cov: 22)
  • Exomes 𝑓: 0.0027 (76 hom. 825 hem.)
• Consequence: DMD NM_004006.3 intron
• Scores: Splicing: ADA: 0.0001244
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 0.562
• Publications: 2 publications found

Genes affected

DMD (HGNC:2928): (dystrophin) This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]

DMD Gene-Disease associations (from GenCC):

• Becker muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• dilated cardiomyopathy 3B

  Inheritance: XL Classification: DEFINITIVE Submitted by: Ambry Genetics
• Duchenne and Becker muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• Duchenne muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• progressive muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-32485110-G-C is Benign according to our data. Variant chrX-32485110-G-C is described in ClinVar as Benign. ClinVar VariationId is 94528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004006.3. 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
	DMD	NM_004006.3	MANE Select	c.2623-11C>G		intron	N/A	NP_003997.2	P11532-1
	DMD	NM_004009.3		c.2611-11C>G		intron	N/A	NP_004000.1	P11532
	DMD	NM_000109.4		c.2599-11C>G		intron	N/A	NP_000100.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMD	ENST00000357033.9	TSL:1 MANE Select	c.2623-11C>G		intron	N/A	ENSP00000354923.3	P11532-1
	DMD	ENST00000378677.6	TSL:5	c.2611-11C>G		intron	N/A	ENSP00000367948.2	P11532-11
	DMD	ENST00000420596.5	TSL:5	c.94-119911C>G		intron	N/A	ENSP00000399897.1	Q14172

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 2663 AN: 111465 Hom.: 80 Cov.: 22

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0127

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00150

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.000414

Gnomad OTH AF: 0.0147

GnomAD2 exomes AF: 0.00745 AC: 1365 AN: 183157 AF XY: 0.00502

Gnomad AFR exome AF: 0.0877

Gnomad AMR exome AF: 0.00522

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000626

Gnomad NFE exome AF: 0.000428

Gnomad OTH exome AF: 0.00642

GnomAD4 exome AF: 0.00275 AC: 2999 AN: 1090682 Hom.: 76 Cov.: 30 AF XY: 0.00231 AC XY: 825 AN XY: 356428

African (AFR) AF: 0.0823 AC: 2162 AN: 26261

American (AMR) AF: 0.00651 AC: 229 AN: 35189

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19340

East Asian (EAS) AF: 0.00 AC: 0 AN: 30150

South Asian (SAS) AF: 0.000204 AC: 11 AN: 53928

European-Finnish (FIN) AF: 0.000148 AC: 6 AN: 40492

Middle Eastern (MID) AF: 0.00754 AC: 31 AN: 4111

European-Non Finnish (NFE) AF: 0.000294 AC: 246 AN: 835346

Other (OTH) AF: 0.00685 AC: 314 AN: 45865

GnomAD4 genome AF: 0.0239 AC: 2666 AN: 111517 Hom.: 81 Cov.: 22 AF XY: 0.0201 AC XY: 678 AN XY: 33721

African (AFR) AF: 0.0811 AC: 2485 AN: 30653

American (AMR) AF: 0.0127 AC: 132 AN: 10432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3559

South Asian (SAS) AF: 0.00150 AC: 4 AN: 2660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6021

Middle Eastern (MID) AF: 0.00459 AC: 1 AN: 218

European-Non Finnish (NFE) AF: 0.000414 AC: 22 AN: 53119

Other (OTH) AF: 0.0145 AC: 22 AN: 1518

Alfa AF: 0.0125 Hom.: 55

Bravo AF: 0.0284

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	4	not provided (4)
-	-	1	Dilated cardiomyopathy 3B (1)
-	-	1	Duchenne muscular dystrophy (1)
-	-	1	Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.38
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.086
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: rs1028360; hg19: chrX-32503227;