chr15-78596440-A-ATT

Variant names:

• chr15-78596440-A-ATT
• rs71148543
• NM_000743.5:c.*162_*163dupAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000743.5(CHRNA3):​c.*162_*163dupAA 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: not found (cov: 0)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: CHRNA3 NM_000743.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.998
• Publications: 0 publications found

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]

CHRNA3 Gene-Disease associations (from GenCC):

• urinary bladder, atony of

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.*162_*163dupAA		3_prime_UTR_variant	Exon 6 of 6	ENST00000326828.6	NP_000734.2
CHRNA3	XM_006720382.4	c.*162_*163dupAA		3_prime_UTR_variant	Exon 6 of 6		XP_006720445.1
CHRNA3	NM_001166694.2	c.1390-3251_1390-3250dupAA		intron_variant	Intron 5 of 5		NP_001160166.1
CHRNA3	NR_046313.2	n.1784+98_1784+99dupAA		intron_variant	Intron 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.*162_*163dupAA		3_prime_UTR_variant	Exon 6 of 6	1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7	c.1390-3251_1390-3250dupAA		intron_variant	Intron 5 of 5	1		ENSP00000267951.4
CHRNA3	ENST00000559002.5	n.193+98_193+99dupAA		intron_variant	Intron 1 of 1	1
CHRNA3	ENST00000559658.5	n.*64+98_*64+99dupAA		intron_variant	Intron 6 of 7	2		ENSP00000452896.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000195 AC: 19 AN: 976146 Hom.: 0 Cov.: 0 AF XY: 0.0000301 AC XY: 14 AN XY: 464656

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21596

American (AMR) AF: 0.000108 AC: 1 AN: 9254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13140

East Asian (EAS) AF: 0.0000478 AC: 1 AN: 20906

South Asian (SAS) AF: 0.0000692 AC: 2 AN: 28908

European-Finnish (FIN) AF: 0.0000482 AC: 1 AN: 20742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2700

European-Non Finnish (NFE) AF: 0.0000159 AC: 13 AN: 818884

Other (OTH) AF: 0.0000250 AC: 1 AN: 40016

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs71148543; hg19: chr15-78888782;