15-78661443-C-T

Position:

• chr15-78661443-C-T

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

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

(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=-0.72).
• 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/exons	MANE	Protein	UniProt
CHRNB4	XM_011521186.3	c.-1251G>A		5_prime_UTR_variant	1/10		XP_011519488.1
CHRNB4	XM_011521187.3	c.-1157G>A		5_prime_UTR_variant	1/9		XP_011519489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPL18P11	ENST00000494933.1	n.134G>A		non_coding_transcript_exon_variant	1/1
	ENST00000569846.1	n.275C>T		non_coding_transcript_exon_variant	2/4	4
CHRNB4	ENST00000560511.5	n.229-5780G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.0495

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.00125

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.231

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

Gnomad4 AFR AF: 0.0523

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.230

Alfa AF: 0.281 Hom.: 9192

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17487514; hg19: chr15-78953785;