rs225604

Positions:

• chr6-142131429-G-A
• chr6-142131429-G-C

Variant summary

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

The NM_002511.4(NMBR):​c.-664+15615C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,972 control chromosomes in the GnomAD database, including 13,091 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 0.41 (13091 hom., cov: 32)
• Consequence: NMBR NM_002511.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NMBR	NM_002511.4	c.-664+15615C>T		intron_variant		ENST00000258042.2
NMBR	NM_001324307.2	c.-23+11127C>T		intron_variant
NMBR	NM_001324308.2	c.-23+15615C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NMBR	ENST00000258042.2	c.-664+15615C>T		intron_variant		1	NM_002511.4	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61685 AN: 151854 Hom.: 13083 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.406 AC: 61721 AN: 151972 Hom.: 13091 Cov.: 32 AF XY: 0.400 AC XY: 29738 AN XY: 74256

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.414

Alfa AF: 0.317 Hom.: 1223

Bravo AF: 0.393

Asia WGS AF: 0.365 AC: 1273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs225604; hg19: chr6-142452566;