15-78618523-ATG-A

Position:

• chr15-78618523-ATG-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000743.5(CHRNA3):​c.267+92_267+93del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,458,268 control chromosomes in the GnomAD database, including 66 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (30 hom.)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1853/152228) while in subpopulation AFR AF= 0.0407 (1689/41506). AF 95% confidence interval is 0.0391. There are 36 homozygotes in gnomad4. There are 848 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA3	NM_000743.5	c.267+92_267+93del		intron_variant		ENST00000326828.6
CHRNA3	NM_001166694.2	c.267+92_267+93del		intron_variant
CHRNA3	XM_006720382.4	c.66+92_66+93del		intron_variant
CHRNA3	NR_046313.2	n.469+92_469+93del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA3	ENST00000326828.6	c.267+92_267+93del		intron_variant		1	NM_000743.5	P1
CHRNA3	ENST00000348639.7	c.267+92_267+93del		intron_variant		1
CHRNA3	ENST00000561128.1	n.354_355del		non_coding_transcript_exon_variant	3/3	2
CHRNA3	ENST00000559658.5	c.267+92_267+93del		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1852 AN: 152108 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00150 AC: 1957 AN: 1306040 Hom.: 30 AF XY: 0.00131 AC XY: 862 AN XY: 656046

Gnomad4 AFR exome AF: 0.0424

Gnomad4 AMR exome AF: 0.00385

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.000124

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.000270

Gnomad4 OTH exome AF: 0.00375

GnomAD4 genome AF: 0.0122 AC: 1853 AN: 152228 Hom.: 36 Cov.: 32 AF XY: 0.0114 AC XY: 848 AN XY: 74426

Gnomad4 AFR AF: 0.0407

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.00945

Alfa AF: 0.0112 Hom.: 2

Bravo AF: 0.0141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs71581740; hg19: chr15-78910865;