rs4305737

Variant names:

• chr6-144730458-G-A
• rs4305737
• NM_007124.3:c.7911G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-144730458-G-A
• chr6-144730458-G-C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_007124.3(UTRN):​c.7911G>A​(p.Glu2637Glu) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.07
• Publications: 18 publications found

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 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
UTRN	NM_007124.3	c.7911G>A	p.Glu2637Glu	synonymous_variant	Exon 54 of 75	ENST00000367545.8	NP_009055.2
UTRN	NM_001375323.1	c.576G>A	p.Glu192Glu	synonymous_variant	Exon 4 of 25		NP_001362252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTRN	ENST00000367545.8	c.7911G>A	p.Glu2637Glu	synonymous_variant	Exon 54 of 75	5	NM_007124.3	ENSP00000356515.3
UTRN	ENST00000367526.8	c.576G>A	p.Glu192Glu	synonymous_variant	Exon 4 of 25	5		ENSP00000356496.4
UTRN	ENST00000367524.8	c.576G>A	p.Glu192Glu	synonymous_variant	Exon 4 of 24	3		ENSP00000356494.4

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69474 AN: 151866 Hom.: 21114 Cov.: 32

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

GnomAD2 exomes AF: 0.415 AC: 102446 AN: 246798 AF XY: 0.393

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 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.: 32 AF XY: 0.303 AC XY: 219196 AN XY: 724358

African (AFR) AF: 0.825 AC: 27296 AN: 33086

American (AMR) AF: 0.658 AC: 29078 AN: 44178

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 9711 AN: 25944

East Asian (EAS) AF: 0.872 AC: 34201 AN: 39200

South Asian (SAS) AF: 0.439 AC: 37519 AN: 85540

European-Finnish (FIN) AF: 0.216 AC: 11515 AN: 53258

Middle Eastern (MID) AF: 0.405 AC: 2322 AN: 5740

European-Non Finnish (NFE) AF: 0.240 AC: 266221 AN: 1108742

Other (OTH) AF: 0.354 AC: 21306 AN: 60116

GnomAD4 genome AF: 0.458 AC: 69600 AN: 151984 Hom.: 21177 Cov.: 32 AF XY: 0.461 AC XY: 34280 AN XY: 74294

African (AFR) AF: 0.806 AC: 33430 AN: 41464

American (AMR) AF: 0.543 AC: 8287 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1313 AN: 3466

East Asian (EAS) AF: 0.870 AC: 4489 AN: 5160

South Asian (SAS) AF: 0.465 AC: 2239 AN: 4820

European-Finnish (FIN) AF: 0.219 AC: 2310 AN: 10550

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16253 AN: 67968

Other (OTH) AF: 0.448 AC: 942 AN: 2102

Alfa AF: 0.302 Hom.: 28124

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

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.1
DANN	Benign	0.51
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4305737; hg19: chr6-145051594; COSMIC: COSV108202352;