6-144435730-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007124.3(UTRN):c.856-205A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,190 control chromosomes in the GnomAD database, including 1,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1272 hom., cov: 32)
• Consequence: UTRN NM_007124.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.119

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-144435730-A-C is Benign according to our data. Variant chr6-144435730-A-C is described in ClinVar as [Benign]. Clinvar id is 1249127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTRN	NM_007124.3	c.856-205A>C		intron_variant		ENST00000367545.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTRN	ENST00000367545.8	c.856-205A>C		intron_variant		5	NM_007124.3	P1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16874 AN: 152072 Hom.: 1267 Cov.: 32

Gnomad AFR AF: 0.0293

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.0875

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.111 AC: 16884 AN: 152190 Hom.: 1272 Cov.: 32 AF XY: 0.112 AC XY: 8326 AN XY: 74406

Gnomad4 AFR AF: 0.0292

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.0870

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.127

Alfa AF: 0.0891 Hom.: 162

Bravo AF: 0.116

Asia WGS AF: 0.170 AC: 592 AN: 3478

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

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.15
Dann	Benign	0.76

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: rs9403562; hg19: chr6-144756866;