rs8192479

chr15-78617056-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_000743.5(CHRNA3):c.345G>A(p.Lys115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,613,480 control chromosomes in the GnomAD database, including 274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (19 hom., cov: 32)
  • Exomes 𝑓: 0.017 (255 hom.)
• Consequence: CHRNA3 NM_000743.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.957

Genes affected

CHRNA3 (HGNC:1957): (cholinergic receptor nicotinic alpha 3 subunit) This locus encodes a member of the nicotinic acetylcholine receptor family of proteins. Members of this family of proteins form pentameric complexes comprised of both alpha and beta subunits. This locus encodes an alpha-type subunit, as it contains characteristic adjacent cysteine residues. The encoded protein is a ligand-gated ion channel that likely plays a role in neurotransmission. Polymorphisms in this gene have been associated with an increased risk of smoking initiation and an increased susceptibility to lung cancer. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 15-78617056-C-T is Benign according to our data. Variant chr15-78617056-C-T is described in ClinVar as [Benign]. Clinvar id is 2123513.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.957 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.013 (1974/152340) while in subpopulation NFE AF= 0.0209 (1420/68040). AF 95% confidence interval is 0.02. There are 19 homozygotes in gnomad4. There are 897 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA3	NM_000743.5	c.345G>A	p.Lys115=	synonymous_variant	4/6	ENST00000326828.6
CHRNA3	NM_001166694.2	c.345G>A	p.Lys115=	synonymous_variant	4/6
CHRNA3	XM_006720382.4	c.144G>A	p.Lys48=	synonymous_variant	4/6
CHRNA3	NR_046313.2	n.547G>A		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA3	ENST00000326828.6	c.345G>A	p.Lys115=	synonymous_variant	4/6	1	NM_000743.5	P1
CHRNA3	ENST00000348639.7	c.345G>A	p.Lys115=	synonymous_variant	4/6	1
CHRNA3	ENST00000559658.5	c.345G>A	p.Lys115=	synonymous_variant, NMD_transcript_variant	4/8	2

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1974 AN: 152222 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00321

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.0129 AC: 3225 AN: 250890 Hom.: 34 AF XY: 0.0130 AC XY: 1758 AN XY: 135598

Gnomad AFR exome AF: 0.00327

Gnomad AMR exome AF: 0.00310

Gnomad ASJ exome AF: 0.00905

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00154

Gnomad FIN exome AF: 0.0281

Gnomad NFE exome AF: 0.0199

Gnomad OTH exome AF: 0.0108

GnomAD4 exome AF: 0.0173 AC: 25349 AN: 1461140 Hom.: 255 Cov.: 30 AF XY: 0.0170 AC XY: 12355 AN XY: 726910

Gnomad4 AFR exome AF: 0.00281

Gnomad4 AMR exome AF: 0.00396

Gnomad4 ASJ exome AF: 0.00995

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00160

Gnomad4 FIN exome AF: 0.0276

Gnomad4 NFE exome AF: 0.0200

Gnomad4 OTH exome AF: 0.0164

GnomAD4 genome AF: 0.0130 AC: 1974 AN: 152340 Hom.: 19 Cov.: 32 AF XY: 0.0120 AC XY: 897 AN XY: 74488

Gnomad4 AFR AF: 0.00320

Gnomad4 AMR AF: 0.00693

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00165

Gnomad4 FIN AF: 0.0241

Gnomad4 NFE AF: 0.0209

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.0161 Hom.: 6

Bravo AF: 0.0114

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0185

EpiControl AF: 0.0193

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
Cadd	Benign	13
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8192479; hg19: chr15-78909398;