rs6926279

Positions:

• chr6-142077965-T-C

Variant summary

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

The NM_002511.4(NMBR):​c.771+590A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,068 control chromosomes in the GnomAD database, including 19,557 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 0.50 (19557 hom., cov: 32)
• Consequence: NMBR NM_002511.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NMBR	NM_002511.4	c.771+590A>G		intron_variant		ENST00000258042.2	NP_002502.2
NMBR	NM_001324307.2	c.327+590A>G		intron_variant			NP_001311236.1
NMBR	NM_001324308.2	c.327+590A>G		intron_variant			NP_001311237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NMBR	ENST00000258042.2	c.771+590A>G		intron_variant		1	NM_002511.4	ENSP00000258042	P1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76054 AN: 151950 Hom.: 19544 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.500 AC: 76110 AN: 152068 Hom.: 19557 Cov.: 32 AF XY: 0.504 AC XY: 37464 AN XY: 74318

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.504

Alfa AF: 0.481 Hom.: 3042

Bravo AF: 0.512

Asia WGS AF: 0.533 AC: 1850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.68

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: rs6926279; hg19: chr6-142399102;