Variant rs4305737 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_007124.3(UTRN):c.7911G>A(p.Glu2637=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,607,788 control chromosomes in the GnomAD database, including 106,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 21177 hom., cov: 32)

Exomes 𝑓: 0.30 ( 84902 hom. )

Consequence

UTRN
NM_007124.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.07

Variant links:

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]

UTRN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 6-144730458-G-A is Benign according to our data. Variant chr6-144730458-G-A is described in ClinVar as [Benign]. Clinvar id is 1266647.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTRN	NM_007124.3 linkuse as main transcript	c.7911G>A	p.Glu2637=	synonymous_variant	54/75	ENST00000367545.8	NP_009055.2
UTRN	NM_001375323.1 linkuse as main transcript	c.576G>A	p.Glu192=	synonymous_variant	4/25		NP_001362252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTRN	ENST00000367545.8 linkuse as main transcript	c.7911G>A	p.Glu2637=	synonymous_variant	54/75	5	NM_007124.3	ENSP00000356515	P1	P46939-1
UTRN	ENST00000367526.8 linkuse as main transcript	c.576G>A	p.Glu192=	synonymous_variant	4/25	5		ENSP00000356496
UTRN	ENST00000367524.8 linkuse as main transcript	c.576G>A	p.Glu192=	synonymous_variant	4/24	3		ENSP00000356494

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69474

AN:

151866

Hom.:

21114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.806

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.543

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.870

Gnomad SAS

AF:

0.466

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.414

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.444

GnomAD3 exomes

AF:

0.415

AC:

102446

AN:

246798

Hom.:

28419

AF XY:

0.393

AC XY:

52621

AN XY:

133738

show subpopulations

Gnomad AFR exome

AF:

0.819

Gnomad AMR exome

AF:

0.675

Gnomad ASJ exome

AF:

0.378

Gnomad EAS exome

AF:

0.878

Gnomad SAS exome

AF:

0.444

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.242

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.302

AC:

439169

AN:

1455804

Hom.:

84902

Cov.:

AF XY:

0.303

AC XY:

219196

AN XY:

724358

show subpopulations

Gnomad4 AFR exome

AF:

0.825

Gnomad4 AMR exome

AF:

0.658

Gnomad4 ASJ exome

AF:

0.374

Gnomad4 EAS exome

AF:

0.872

Gnomad4 SAS exome

AF:

0.439

Gnomad4 FIN exome

AF:

0.216

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.354

GnomAD4 genome

AF:

0.458

AC:

69600

AN:

151984

Hom.:

21177

Cov.:

AF XY:

0.461

AC XY:

34280

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.806

Gnomad4 AMR

AF:

0.543

Gnomad4 ASJ

AF:

0.379

Gnomad4 EAS

AF:

0.870

Gnomad4 SAS

AF:

0.465

Gnomad4 FIN

AF:

0.219

Gnomad4 NFE

AF:

0.239

Gnomad4 OTH

AF:

0.448

Alfa

AF:

0.289

Hom.:

12541

Bravo

AF:

0.502

Asia WGS

AF:

0.674

AC:

2341

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

4.1

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over