X-31875745-C-T

Position:

• chrX-31875745-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000357033.9(DMD):​c.6913-372G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0087 in 112,151 control chromosomes in the GnomAD database, including 8 homozygotes. There are 275 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 0.0087 (8 hom., 275 hem., cov: 23)
• Consequence: DMD ENST00000357033.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0087 (976/112151) while in subpopulation AFR AF= 0.0263 (814/30932). AF 95% confidence interval is 0.0248. There are 8 homozygotes in gnomad4. There are 275 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMD	NM_004006.3	c.6913-372G>A		intron_variant		ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9	c.6913-372G>A		intron_variant		1	NM_004006.3	ENSP00000354923	P4

Frequencies

GnomAD3 genomes AF: 0.00863 AC: 967 AN: 112095 Hom.: 8 Cov.: 23 AF XY: 0.00782 AC XY: 268 AN XY: 34275

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.00585

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00302

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000301

Gnomad OTH AF: 0.0113

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

GnomAD4 genome AF: 0.00870 AC: 976 AN: 112151 Hom.: 8 Cov.: 23 AF XY: 0.00801 AC XY: 275 AN XY: 34341

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.00302

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00146

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000301

Gnomad4 OTH AF: 0.0112

Alfa AF: 0.00648 Hom.: 20

Bravo AF: 0.0107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.49
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs16989902; hg19: chrX-31893862;