rs8042374

Variant names:

• chr15-78615690-A-G
• rs8042374
• NM_000743.5:c.377+1334T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-78615690-A-G
• chr15-78615690-A-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000743.5(CHRNA3):​c.377+1334T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 150,978 control chromosomes in the GnomAD database, including 7,874 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7874 hom., cov: 30)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.596
• Publications: 108 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-78615690-A-G is Benign according to our data. Variant chr15-78615690-A-G is described in ClinVar as Benign. ClinVar VariationId is 2143410.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 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+1334T>C		intron	N/A	NP_000734.2
	CHRNA3	NM_001166694.2		c.377+1334T>C		intron	N/A	NP_001160166.1	P32297-3
	CHRNA3	NR_046313.2		n.579+1334T>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+1334T>C		intron	N/A	ENSP00000315602.5	P32297-2
	CHRNA3	ENST00000348639.7	TSL:1	c.377+1334T>C		intron	N/A	ENSP00000267951.4	P32297-3
	CHRNA3	ENST00000893003.1		c.509+1334T>C		intron	N/A	ENSP00000563062.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 44983 AN: 150862 Hom.: 7848 Cov.: 30

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.298 AC: 45049 AN: 150978 Hom.: 7874 Cov.: 30 AF XY: 0.306 AC XY: 22539 AN XY: 73656

African (AFR) AF: 0.296 AC: 12141 AN: 41076

American (AMR) AF: 0.474 AC: 7152 AN: 15096

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3464

East Asian (EAS) AF: 0.710 AC: 3606 AN: 5078

South Asian (SAS) AF: 0.448 AC: 2153 AN: 4810

European-Finnish (FIN) AF: 0.285 AC: 2920 AN: 10258

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15397 AN: 67888

Other (OTH) AF: 0.303 AC: 639 AN: 2106

Alfa AF: 0.258 Hom.: 20394

Bravo AF: 0.316

Asia WGS AF: 0.571 AC: 1984 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		0.60
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: rs8042374; hg19: chr15-78908032; COSMIC: COSV58774145; COSMIC: COSV58774145;