rs225601

Positions:

• chr6-142129140-C-T

Variant summary

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

The NM_002511.4(NMBR):​c.-664+17904G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 150,444 control chromosomes in the GnomAD database, including 11,946 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 0.39 (11946 hom., cov: 28)
• Consequence: NMBR NM_002511.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531

Genes affected

NMBR (HGNC:7843): (neuromedin B receptor) This gene encodes a 7-transmembrane G protein-coupled receptor that binds neuromedin B, which is a growth factor and mitogen for gastrointestinal epithelial tissue and for normal and neoplastic lung. This receptor may play a role in smooth muscle contraction, neuronal responses, and the regulation of cell growth. Antagonists of this receptor have a potential therapeutic use in inhibiting tumor cell growth. Polymorphisms in this gene may be associated with a susceptibility for schizophrenia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMBR	NM_002511.4	c.-664+17904G>A		intron_variant		ENST00000258042.2	NP_002502.2
NMBR	NM_001324307.2	c.-23+13416G>A		intron_variant			NP_001311236.1
NMBR	NM_001324308.2	c.-23+17904G>A		intron_variant			NP_001311237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMBR	ENST00000258042.2	c.-664+17904G>A		intron_variant		1	NM_002511.4	ENSP00000258042	P1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58317 AN: 150326 Hom.: 11941 Cov.: 28

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.388 AC: 58345 AN: 150444 Hom.: 11946 Cov.: 28 AF XY: 0.381 AC XY: 27950 AN XY: 73418

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.385

Alfa AF: 0.435 Hom.: 2970

Bravo AF: 0.378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs225601; hg19: chr6-142450277;