6-144624694-C-T

Position:

• chr6-144624694-C-T

Variant summary

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

The NM_007124.3(UTRN):​c.7479+47406C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 151,960 control chromosomes in the GnomAD database, including 32,739 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 0.65 (32739 hom., cov: 31)
• Consequence: UTRN NM_007124.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTRN	NM_007124.3	c.7479+47406C>T		intron_variant		ENST00000367545.8	NP_009055.2
UTRN	NM_001375323.1	c.144+41094C>T		intron_variant			NP_001362252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTRN	ENST00000367545.8	c.7479+47406C>T		intron_variant		5	NM_007124.3	ENSP00000356515.3
UTRN	ENST00000367526.8	c.144+41094C>T		intron_variant		5		ENSP00000356496.4
UTRN	ENST00000367524.8	c.144+41094C>T		intron_variant		3		ENSP00000356494.4

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98878 AN: 151842 Hom.: 32697 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.651 AC: 98979 AN: 151960 Hom.: 32739 Cov.: 31 AF XY: 0.657 AC XY: 48764 AN XY: 74258

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.660

Alfa AF: 0.608 Hom.: 57833

Bravo AF: 0.664

Asia WGS AF: 0.782 AC: 2721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.1
DANN	Benign	0.29

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: rs951573; hg19: chr6-144945830;