rs2748314

Variant names:

• chrX-32755366-G-A
• rs2748314
• NM_004006.3:c.649+54127C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-32755366-G-A
• chrX-32755366-G-C
• chrX-32755366-G-T

Variant summary

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

The NM_004006.3(DMD):​c.649+54127C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 109,743 control chromosomes in the GnomAD database, including 6,611 homozygotes. There are 11,268 hemizygotes in GnomAD. 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 0.37 (6611 hom., 11268 hem., cov: 22)
• Consequence: DMD NM_004006.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 3 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-AS3 (HGNC:40185): (DMD antisense RNA 3)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 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.649+54127C>T		intron	N/A	NP_003997.2	P11532-1
	DMD	NM_004009.3		c.637+54127C>T		intron	N/A	NP_004000.1	P11532
	DMD	NM_000109.4		c.625+54127C>T		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.649+54127C>T		intron	N/A	ENSP00000354923.3	P11532-1
	DMD	ENST00000288447.9	TSL:1	c.625+54127C>T		intron	N/A	ENSP00000288447.4	Q4G0X0
	DMD	ENST00000447523.1	TSL:1	c.246+67929C>T		intron	N/A	ENSP00000395904.1	Q14174

Frequencies

GnomAD3 genomes AF: 0.369 AC: 40485 AN: 109693 Hom.: 6612 Cov.: 22

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.369 AC: 40514 AN: 109743 Hom.: 6611 Cov.: 22 AF XY: 0.351 AC XY: 11268 AN XY: 32091

African (AFR) AF: 0.622 AC: 18741 AN: 30121

American (AMR) AF: 0.355 AC: 3630 AN: 10214

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 847 AN: 2630

East Asian (EAS) AF: 0.275 AC: 942 AN: 3426

South Asian (SAS) AF: 0.424 AC: 1102 AN: 2600

European-Finnish (FIN) AF: 0.200 AC: 1130 AN: 5649

Middle Eastern (MID) AF: 0.377 AC: 78 AN: 207

European-Non Finnish (NFE) AF: 0.253 AC: 13324 AN: 52724

Other (OTH) AF: 0.385 AC: 575 AN: 1492

Alfa AF: 0.279 Hom.: 18999

Bravo AF: 0.390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.47
DANN	Benign	0.56
PhyloP100		-0.30
Mutation Taster		=100/0	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: rs2748314; hg19: chrX-32773483;