rs2473130

Positions:

• chr6-144290308-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007124.3(UTRN):​c.-92-1429T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 152,286 control chromosomes in the GnomAD database, including 655 homozygotes. 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 0.092 (655 hom., cov: 32)
• Consequence: UTRN NM_007124.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.553

Genes affected

UTRN (HGNC:12635): (utrophin) This gene shares both structural and functional similarities with the dystrophin gene. It contains an actin-binding N-terminus, a triple coiled-coil repeat central region, and a C-terminus that consists of protein-protein interaction motifs which interact with dystroglycan protein components. The protein encoded by this gene is located at the neuromuscular synapse and myotendinous junctions, where it participates in post-synaptic membrane maintenance and acetylcholine receptor clustering. Mouse studies suggest that this gene may serve as a functional substitute for the dystrophin gene and therefore, may serve as a potential therapeutic alternative to muscular dystrophy which is caused by mutations in the dystrophin gene. Alternative splicing of the utrophin gene has been described; however, the full-length nature of these variants has not yet been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -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 = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTRN	NM_007124.3	c.-92-1429T>C		intron_variant		ENST00000367545.8	NP_009055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTRN	ENST00000367545.8	c.-92-1429T>C		intron_variant		5	NM_007124.3	ENSP00000356515	P1

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 14017 AN: 152168 Hom.: 651 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0769

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0627

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.0685

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0890

Gnomad OTH AF: 0.0975

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

GnomAD4 genome AF: 0.0922 AC: 14037 AN: 152286 Hom.: 655 Cov.: 32 AF XY: 0.0892 AC XY: 6646 AN XY: 74468

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0767

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0624

Gnomad4 SAS AF: 0.0464

Gnomad4 FIN AF: 0.0685

Gnomad4 NFE AF: 0.0890

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0974 Hom.: 147

Bravo AF: 0.0937

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2473130; hg19: chr6-144611444;