rs16970006

Positions:

• chr15-78677917-T-C
• chr15-78677917-T-G

Variant summary

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

The ENST00000569846.1(ENSG00000290426):​n.367-14765T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 152,282 control chromosomes in the GnomAD database, including 1,263 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 0.092 (1263 hom., cov: 31)
• Consequence: ENST00000569846.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848

Genes affected

(HGNC:):

CHRNB4 (HGNC:1964): (cholinergic receptor nicotinic beta 4 subunit) This gene is found within a conserved gene cluster and encodes one of the beta subunits of the nicotinic acetylcholine receptor (nAChRs) superfamily which form ligand-gated ion channels with a central pore that forms a cation channel. Neuronal nAChRs are pentameric structures that can be either homomeric or heteromeric, with heteromeric structures containing both alpha and beta subunits. Each subunit contains an extracellular amino terminus and four transmembrane domains. Nicotine is one of the agonists that binds to the receptor. Variants in this gene have been associated with nicotine dependence and lung cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 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
	ENST00000569846.1	n.367-14765T>C		intron_variant, non_coding_transcript_variant		4
CHRNB4	ENST00000560511.5	n.229-22254A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14060 AN: 152162 Hom.: 1257 Cov.: 31

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0924 AC: 14077 AN: 152282 Hom.: 1263 Cov.: 31 AF XY: 0.100 AC XY: 7473 AN XY: 74436

Gnomad4 AFR AF: 0.0179

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.0736

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0842 Hom.: 1306

Bravo AF: 0.0970

Asia WGS AF: 0.272 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.19
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16970006; hg19: chr15-78970259;