6-144624694-C-T

Variant names:

• chr6-144624694-C-T
• rs951573
• NM_007124.3:c.7479+47406C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007124.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTRN	NM_007124.3	MANE Select	c.7479+47406C>T		intron	N/A	NP_009055.2	P46939-1
	UTRN	NM_001375323.1		c.144+41094C>T		intron	N/A	NP_001362252.1	Q5T097

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTRN	ENST00000367545.8	TSL:5 MANE Select	c.7479+47406C>T		intron	N/A	ENSP00000356515.3	P46939-1
	UTRN	ENST00000367526.8	TSL:5	c.144+41094C>T		intron	N/A	ENSP00000356496.4	Q5T097
	UTRN	ENST00000367524.8	TSL:3	c.144+41094C>T		intron	N/A	ENSP00000356494.4	H0Y337

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

African (AFR) AF: 0.714 AC: 29598 AN: 41456

American (AMR) AF: 0.735 AC: 11232 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2228 AN: 3464

East Asian (EAS) AF: 0.855 AC: 4404 AN: 5150

South Asian (SAS) AF: 0.754 AC: 3635 AN: 4820

European-Finnish (FIN) AF: 0.558 AC: 5878 AN: 10538

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39893 AN: 67936

Other (OTH) AF: 0.660 AC: 1392 AN: 2108

Alfa AF: 0.611 Hom.: 120525

Bravo AF: 0.664

Asia WGS AF: 0.782 AC: 2721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.1
DANN	Benign	0.29
PhyloP100		0.56
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: rs951573; hg19: chr6-144945830;