15-78596440-ATTT-ATTTT

Variant names:

• chr15-78596440-A-AT
• rs71148543
• NM_000743.5:c.*163dupA

Variant summary

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

The NM_000743.5(CHRNA3):​c.*163dupA 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 0.00087 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0073 (2 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.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000873 (131/149986) while in subpopulation NFE AF= 0.00104 (70/67270). AF 95% confidence interval is 0.000844. There are 0 homozygotes in gnomad4. There are 59 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 rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.*163dupA		3_prime_UTR_variant	Exon 6 of 6	ENST00000326828.6	NP_000734.2
CHRNA3	XM_006720382.4	c.*163dupA		3_prime_UTR_variant	Exon 6 of 6		XP_006720445.1
CHRNA3	NM_001166694.2	c.1390-3250dupA		intron_variant	Intron 5 of 5		NP_001160166.1
CHRNA3	NR_046313.2	n.1784+99dupA		intron_variant	Intron 6 of 7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000874 AC: 131 AN: 149880 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000880

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000664

Gnomad ASJ AF: 0.000581

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000841

Gnomad FIN AF: 0.000200

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.00243

GnomAD4 exome AF: 0.00727 AC: 6872 AN: 944894 Hom.: 2 Cov.: 0 AF XY: 0.00742 AC XY: 3338 AN XY: 449906

Gnomad4 AFR exome AF: 0.00422

Gnomad4 AMR exome AF: 0.00707

Gnomad4 ASJ exome AF: 0.0117

Gnomad4 EAS exome AF: 0.00245

Gnomad4 SAS exome AF: 0.00727

Gnomad4 FIN exome AF: 0.0142

Gnomad4 NFE exome AF: 0.00715

Gnomad4 OTH exome AF: 0.00879

GnomAD4 genome AF: 0.000873 AC: 131 AN: 149986 Hom.: 0 Cov.: 0 AF XY: 0.000806 AC XY: 59 AN XY: 73198

Gnomad4 AFR AF: 0.000878

Gnomad4 AMR AF: 0.000663

Gnomad4 ASJ AF: 0.000581

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000842

Gnomad4 FIN AF: 0.000200

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.00240

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;