4-55601047-A-G

Position:

• chr4-55601047-A-G

Variant summary

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

The NM_006681.4(NMU):​c.436-472T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,078 control chromosomes in the GnomAD database, including 2,434 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 0.17 (2434 hom., cov: 32)
• Consequence: NMU NM_006681.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753

Genes affected

NMU (HGNC:7859): (neuromedin U) This gene encodes a member of the neuromedin family of neuropeptides. The encoded protein is a precursor that is proteolytically processed to generate a biologically active neuropeptide that plays a role in pain, stress, immune-mediated inflammatory diseases and feeding regulation. Increased expression of this gene was observed in renal, pancreatic and lung cancers. Alternative splicing results in multiple transcript variants encoding different isoforms. Some of these isoforms may undergo similar processing to generate the mature peptide. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMU	NM_006681.4	c.436-472T>C		intron_variant		ENST00000264218.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NMU	ENST00000264218.7	c.436-472T>C		intron_variant		1	NM_006681.4	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26379 AN: 151962 Hom.: 2430 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.174 AC: 26398 AN: 152078 Hom.: 2434 Cov.: 32 AF XY: 0.176 AC XY: 13067 AN XY: 74336

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0923

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.163

Alfa AF: 0.188 Hom.: 996

Bravo AF: 0.160

Asia WGS AF: 0.198 AC: 680 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.69
DANN	Benign	0.47

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: rs13434995; hg19: chr4-56467214;