ENST00000559849.5:n.-708-95G>A

Variant names:

• chr15-78661335-G-T
• ENST00000494933.1:n.242C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000846725.1(ENSG00000290426):​n.201G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000290426 ENST00000846725.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59
• Publications: 0 publications found

Genes affected

RPL18P11 (HGNC:35742): (ribosomal protein L18 pseudogene 11)

ENSG00000290426 (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]

CHRNB4 Gene-Disease associations (from GenCC):

• lung cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL18P11		n.78661335G>T		intragenic_variant
CHRNB4	XM_011521186.3	c.-1143C>A		5_prime_UTR_variant	Exon 1 of 10		XP_011519488.1
CHRNB4	XM_011521187.3	c.-1049C>A		5_prime_UTR_variant	Exon 1 of 9		XP_011519489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL18P11	ENST00000494933.1	n.242C>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000290426	ENST00000846725.1	n.201G>T		non_coding_transcript_exon_variant	Exon 1 of 6
ENSG00000290426	ENST00000846726.1	n.201G>T		non_coding_transcript_exon_variant	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 418432 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 234066

African (AFR) AF: 0.00 AC: 0 AN: 11702

American (AMR) AF: 0.00 AC: 0 AN: 34076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12030

East Asian (EAS) AF: 0.00 AC: 0 AN: 18008

South Asian (SAS) AF: 0.00 AC: 0 AN: 62138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1488

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 225298

Other (OTH) AF: 0.00 AC: 0 AN: 20400

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.8
DANN	Benign	0.76
PhyloP100		2.6

Splicing

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

Other links and lift over

hg19: chr15-78953677;