rs11637630

Variant names:

• chr15-78607377-G-A
• rs11637630
• NM_000743.5:c.378-5113C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-78607377-G-A
• chr15-78607377-G-C
• chr15-78607377-G-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.378-5113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,010 control chromosomes in the GnomAD database, including 38,864 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 0.71 (38858 hom., cov: 31)
  • Exomes 𝑓: 0.67 (6 hom.)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666
• Publications: 35 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.378-5113C>T		intron_variant	Intron 4 of 5	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.378-5113C>T		intron_variant	Intron 4 of 5		NP_001160166.1
CHRNA3	NR_046313.2	n.580-5113C>T		intron_variant	Intron 4 of 7
CHRNA3	XM_006720382.4	c.177-5113C>T		intron_variant	Intron 4 of 5		XP_006720445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.378-5113C>T		intron_variant	Intron 4 of 5	1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7	c.378-5113C>T		intron_variant	Intron 4 of 5	1		ENSP00000267951.4
CHRNA3	ENST00000558903.1	n.84+64C>T		intron_variant	Intron 1 of 1	4
CHRNA3	ENST00000559658.5	n.378-5113C>T		intron_variant	Intron 4 of 7	2		ENSP00000452896.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107516 AN: 151868 Hom.: 38838 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 0.667 AC: 16 AN: 24 Hom.: 6 AF XY: 0.600 AC XY: 12 AN XY: 20

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.857 AC: 12 AN: 14

Other (OTH) AF: 0.375 AC: 3 AN: 8

GnomAD4 genome AF: 0.708 AC: 107569 AN: 151986 Hom.: 38858 Cov.: 31 AF XY: 0.700 AC XY: 52010 AN XY: 74274

African (AFR) AF: 0.700 AC: 29000 AN: 41446

American (AMR) AF: 0.522 AC: 7956 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2721 AN: 3472

East Asian (EAS) AF: 0.536 AC: 2752 AN: 5134

South Asian (SAS) AF: 0.559 AC: 2693 AN: 4818

European-Finnish (FIN) AF: 0.704 AC: 7439 AN: 10562

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52578 AN: 67990

Other (OTH) AF: 0.695 AC: 1468 AN: 2112

Alfa AF: 0.744 Hom.: 17440

Bravo AF: 0.694

Asia WGS AF: 0.517 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.17
DANN	Benign	0.31
PhyloP100		-0.67
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: rs11637630; hg19: chr15-78899719;