chr6-142062945-G-A

Position:

• chr6-142062945-G-A

Variant summary

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

The ENST00000604304.1(ENSG00000270983):​n.229G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,601,878 control chromosomes in the GnomAD database, including 258,978 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 0.64 (33492 hom., cov: 32)
  • Exomes 𝑓: 0.55 (225486 hom.)
• Consequence: ENST00000604304.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

Genes affected

(HGNC:):

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000604304.1	n.229G>A		non_coding_transcript_exon_variant	1/1
NMBR	ENST00000480652.1	n.268-4482C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97857 AN: 151878 Hom.: 33430 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.643

GnomAD4 exome AF: 0.549 AC: 796110 AN: 1449884 Hom.: 225486 Cov.: 33 AF XY: 0.546 AC XY: 393675 AN XY: 721524

Gnomad4 AFR exome AF: 0.865

Gnomad4 AMR exome AF: 0.779

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.887

Gnomad4 SAS exome AF: 0.540

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.521

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.645 AC: 97981 AN: 151994 Hom.: 33492 Cov.: 32 AF XY: 0.650 AC XY: 48291 AN XY: 74284

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.644

Alfa AF: 0.590 Hom.: 3489

Bravo AF: 0.668

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6907175; hg19: chr6-142384082;