rs7177514

Variant names:

• chr15-78615064-C-G
• rs7177514
• NM_000743.5:c.377+1960G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-78615064-C-G
• chr15-78615064-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000743.5(CHRNA3):​c.377+1960G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,018 control chromosomes in the GnomAD database, including 8,071 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (8071 hom., cov: 31)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 23 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

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.377+1960G>C		intron	N/A	NP_000734.2
	CHRNA3	NM_001166694.2		c.377+1960G>C		intron	N/A	NP_001160166.1	P32297-3
	CHRNA3	NR_046313.2		n.579+1960G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA3	ENST00000326828.6	TSL:1 MANE Select	c.377+1960G>C		intron	N/A	ENSP00000315602.5	P32297-2
	CHRNA3	ENST00000348639.7	TSL:1	c.377+1960G>C		intron	N/A	ENSP00000267951.4	P32297-3
	CHRNA3	ENST00000893003.1		c.509+1960G>C		intron	N/A	ENSP00000563062.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45718 AN: 151900 Hom.: 8045 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.299

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.301 AC: 45785 AN: 152018 Hom.: 8071 Cov.: 31 AF XY: 0.309 AC XY: 22989 AN XY: 74298

African (AFR) AF: 0.299 AC: 12396 AN: 41434

American (AMR) AF: 0.477 AC: 7289 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3464

East Asian (EAS) AF: 0.713 AC: 3688 AN: 5176

South Asian (SAS) AF: 0.449 AC: 2163 AN: 4814

European-Finnish (FIN) AF: 0.294 AC: 3114 AN: 10576

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15445 AN: 67960

Other (OTH) AF: 0.306 AC: 647 AN: 2112

Alfa AF: 0.128 Hom.: 203

Bravo AF: 0.317

Asia WGS AF: 0.571 AC: 1984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.98
DANN	Benign	0.40
PhyloP100		-0.017
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7177514; hg19: chr15-78907406;