15-78596440-ATT-AT

Position:

• chr15-78596440-ATT-AT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000743.5(CHRNA3):​c.*163del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (13673 hom., cov: 0)
  • Exomes 𝑓: 0.36 (42247 hom.)
• Consequence: CHRNA3 NM_000743.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.998

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.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA3	NM_000743.5	c.*163del		3_prime_UTR_variant	6/6	ENST00000326828.6
CHRNA3	XM_006720382.4	c.*163del		3_prime_UTR_variant	6/6
CHRNA3	NM_001166694.2	c.1390-3250del		intron_variant
CHRNA3	NR_046313.2	n.1784+99del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA3	ENST00000326828.6	c.*163del		3_prime_UTR_variant	6/6	1	NM_000743.5	P1
CHRNA3	ENST00000348639.7	c.1390-3250del		intron_variant		1
CHRNA3	ENST00000559002.5	n.193+99del		intron_variant, non_coding_transcript_variant		1
CHRNA3	ENST00000559658.5	c.*64+99del		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60229 AN: 149666 Hom.: 13644 Cov.: 0

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.362 AC: 329978 AN: 912316 Hom.: 42247 Cov.: 0 AF XY: 0.362 AC XY: 157177 AN XY: 434686

Gnomad4 AFR exome AF: 0.555

Gnomad4 AMR exome AF: 0.539

Gnomad4 ASJ exome AF: 0.327

Gnomad4 EAS exome AF: 0.741

Gnomad4 SAS exome AF: 0.439

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.403 AC: 60310 AN: 149772 Hom.: 13673 Cov.: 0 AF XY: 0.409 AC XY: 29874 AN XY: 73070

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.396

Bravo AF: 0.422

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: rs71148543; hg19: chr15-78888782;