15-78615690-A-G

Position:

• chr15-78615690-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.377+1334T>C		intron_variant		ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.377+1334T>C		intron_variant			NP_001160166.1
CHRNA3	XM_006720382.4	c.176+1334T>C		intron_variant			XP_006720445.1
CHRNA3	NR_046313.2	n.579+1334T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.377+1334T>C		intron_variant		1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7	c.377+1334T>C		intron_variant		1		ENSP00000267951.4
CHRNA3	ENST00000559658.5	n.377+1334T>C		intron_variant		2		ENSP00000452896.1

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

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.303

Alfa AF: 0.250 Hom.: 8037

Bravo AF: 0.316

Asia WGS AF: 0.571 AC: 1984 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.84

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: rs8042374; hg19: chr15-78908032; COSMIC: COSV58774145; COSMIC: COSV58774145;