rs71148543

Positions:

• chr15-78596440-ATT-A
• chr15-78596440-ATT-AT
• chr15-78596440-ATT-ATTT
• chr15-78596440-ATT-ATTTTTTT

Variant summary

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

The NM_000743.5(CHRNA3):​c.*162_*163del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,120,818 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00025 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0013 (2 hom.)
• Consequence: CHRNA3 NM_000743.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

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 sas. gnomad4 allele frequency = 0.000253 (38/149990) while in subpopulation SAS AF= 0.00568 (27/4752). AF 95% confidence interval is 0.00401. There are 1 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA3	NM_000743.5	c.*162_*163del		3_prime_UTR_variant	6/6	ENST00000326828.6
CHRNA3	XM_006720382.4	c.*162_*163del		3_prime_UTR_variant	6/6
CHRNA3	NM_001166694.2	c.1390-3251_1390-3250del		intron_variant
CHRNA3	NR_046313.2	n.1784+98_1784+99del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA3	ENST00000326828.6	c.*162_*163del		3_prime_UTR_variant	6/6	1	NM_000743.5	P1
CHRNA3	ENST00000348639.7	c.1390-3251_1390-3250del		intron_variant		1
CHRNA3	ENST00000559002.5	n.193+98_193+99del		intron_variant, non_coding_transcript_variant		1
CHRNA3	ENST00000559658.5	c.*64+98_*64+99del		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000260 AC: 39 AN: 149884 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000664

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000583

Gnomad SAS AF: 0.00588

Gnomad FIN AF: 0.0000998

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00135 AC: 1308 AN: 970828 Hom.: 2 AF XY: 0.00147 AC XY: 677 AN XY: 462086

Gnomad4 AFR exome AF: 0.00211

Gnomad4 AMR exome AF: 0.00727

Gnomad4 ASJ exome AF: 0.00253

Gnomad4 EAS exome AF: 0.0151

Gnomad4 SAS exome AF: 0.00817

Gnomad4 FIN exome AF: 0.00238

Gnomad4 NFE exome AF: 0.000617

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome AF: 0.000253 AC: 38 AN: 149990 Hom.: 1 Cov.: 0 AF XY: 0.000355 AC XY: 26 AN XY: 73200

Gnomad4 AFR AF: 0.000122

Gnomad4 AMR AF: 0.0000663

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000584

Gnomad4 SAS AF: 0.00568

Gnomad4 FIN AF: 0.0000998

Gnomad4 NFE AF: 0.0000149

Gnomad4 OTH AF: 0.00

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;