chr15-78661443-C-T

Variant names:

• chr15-78661443-C-T
• rs17487514
• ENST00000494933.1:n.134G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000494933.1(RPL18P11):​n.134G>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 0.213 in 509,896 control chromosomes in the GnomAD database, including 14,274 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 0.19 (3854 hom., cov: 32)
  • Exomes 𝑓: 0.22 (10420 hom.)
• Consequence: RPL18P11 ENST00000494933.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 11 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL18P11		n.78661443C>T		intragenic_variant
CHRNB4	XM_011521186.3	c.-1251G>A		5_prime_UTR_variant	Exon 1 of 10		XP_011519488.1
CHRNB4	XM_011521187.3	c.-1157G>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.134G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000290426	ENST00000569846.2	n.275C>T		non_coding_transcript_exon_variant	Exon 2 of 6	4
ENSG00000290426	ENST00000846725.1	n.309C>T		non_coding_transcript_exon_variant	Exon 1 of 6

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29561 AN: 152058 Hom.: 3852 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.337

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.221 AC: 78985 AN: 357718 Hom.: 10420 Cov.: 0 AF XY: 0.217 AC XY: 43175 AN XY: 198856

African (AFR) AF: 0.0495 AC: 484 AN: 9780

American (AMR) AF: 0.145 AC: 3876 AN: 26776

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 2642 AN: 8890

East Asian (EAS) AF: 0.00125 AC: 21 AN: 16818

South Asian (SAS) AF: 0.122 AC: 6707 AN: 54912

European-Finnish (FIN) AF: 0.168 AC: 4720 AN: 28156

Middle Eastern (MID) AF: 0.306 AC: 363 AN: 1186

European-Non Finnish (NFE) AF: 0.290 AC: 56161 AN: 193844

Other (OTH) AF: 0.231 AC: 4011 AN: 17356

GnomAD4 genome AF: 0.194 AC: 29560 AN: 152178 Hom.: 3854 Cov.: 32 AF XY: 0.186 AC XY: 13843 AN XY: 74400

African (AFR) AF: 0.0523 AC: 2173 AN: 41538

American (AMR) AF: 0.194 AC: 2962 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3470

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5186

South Asian (SAS) AF: 0.117 AC: 562 AN: 4820

European-Finnish (FIN) AF: 0.160 AC: 1688 AN: 10580

Middle Eastern (MID) AF: 0.334 AC: 97 AN: 290

European-Non Finnish (NFE) AF: 0.299 AC: 20329 AN: 67984

Other (OTH) AF: 0.230 AC: 486 AN: 2114

Alfa AF: 0.260 Hom.: 12798

Bravo AF: 0.193

Asia WGS AF: 0.0560 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.7
DANN	Benign	0.72
PhyloP100		0.44

Splicing

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

Other links and lift over

dbSNP: rs17487514; hg19: chr15-78953785;