6-144291828-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_007124.3(UTRN):c.-1G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00818 in 1,610,884 control chromosomes in the GnomAD database, including 844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (87 hom., cov: 33)
  • Exomes 𝑓: 0.0076 (757 hom.)
• Consequence: UTRN NM_007124.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.897

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=-0.39).
• BP6: Variant 6-144291828-G-A is Benign according to our data. Variant chr6-144291828-G-A is described in ClinVar as [Benign]. Clinvar id is 1275590.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTRN	NM_007124.3	c.-1G>A		5_prime_UTR_variant	2/75	ENST00000367545.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTRN	ENST00000367545.8	c.-1G>A		5_prime_UTR_variant	2/75	5	NM_007124.3	P1

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2039 AN: 152226 Hom.: 87 Cov.: 33

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0133

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000852

Gnomad OTH AF: 0.0119

GnomAD3 exomes AF: 0.0188 AC: 4672 AN: 248124 Hom.: 251 AF XY: 0.0167 AC XY: 2240 AN XY: 134060

Gnomad AFR exome AF: 0.0181

Gnomad AMR exome AF: 0.0319

Gnomad ASJ exome AF: 0.00161

Gnomad EAS exome AF: 0.154

Gnomad SAS exome AF: 0.00464

Gnomad FIN exome AF: 0.00930

Gnomad NFE exome AF: 0.000825

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.00764 AC: 11143 AN: 1458540 Hom.: 757 Cov.: 30 AF XY: 0.00741 AC XY: 5379 AN XY: 725460

Gnomad4 AFR exome AF: 0.0167

Gnomad4 AMR exome AF: 0.0286

Gnomad4 ASJ exome AF: 0.000961

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.00589

Gnomad4 FIN exome AF: 0.00941

Gnomad4 NFE exome AF: 0.000338

Gnomad4 OTH exome AF: 0.00933

GnomAD4 genome AF: 0.0134 AC: 2038 AN: 152344 Hom.: 87 Cov.: 33 AF XY: 0.0145 AC XY: 1083 AN XY: 74484

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.0133

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.000852

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.00427 Hom.: 10

Bravo AF: 0.0153

Asia WGS AF: 0.0580 AC: 201 AN: 3478

EpiCase AF: 0.000437

EpiControl AF: 0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	13
Dann	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17073571; hg19: chr6-144612964; COSMIC: COSV62330428;