chr15-78618523-ATG-A

Variant names:

• chr15-78618523-ATG-A
• rs71581740
• NM_000743.5:c.267+92_267+93delCA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000743.5(CHRNA3):​c.267+92_267+93delCA 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
• Publications: 3 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: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000743.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	NM_000743.5	MANE Select	c.267+92_267+93delCA		intron	N/A	NP_000734.2
	CHRNA3	NM_001166694.2		c.267+92_267+93delCA		intron	N/A	NP_001160166.1	P32297-3
	CHRNA3	NR_046313.2		n.469+92_469+93delCA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	ENST00000326828.6	TSL:1 MANE Select	c.267+92_267+93delCA		intron	N/A	ENSP00000315602.5	P32297-2
	CHRNA3	ENST00000348639.7	TSL:1	c.267+92_267+93delCA		intron	N/A	ENSP00000267951.4	P32297-3
	CHRNA3	ENST00000893003.1		c.399+92_399+93delCA		intron	N/A	ENSP00000563062.1

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

African (AFR) AF: 0.0424 AC: 1284 AN: 30290

American (AMR) AF: 0.00385 AC: 162 AN: 42122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24694

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38834

South Asian (SAS) AF: 0.000124 AC: 10 AN: 80828

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52604

Middle Eastern (MID) AF: 0.00725 AC: 29 AN: 4000

European-Non Finnish (NFE) AF: 0.000270 AC: 264 AN: 977734

Other (OTH) AF: 0.00375 AC: 206 AN: 54934

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

African (AFR) AF: 0.0407 AC: 1689 AN: 41506

American (AMR) AF: 0.00680 AC: 104 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68014

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.0112 Hom.: 2

Bravo AF: 0.0141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.065
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs71581740; hg19: chr15-78910865;