Variant rs71148543 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_000743.5(CHRNA3):c.*162_*163del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,120,818 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00025 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

CHRNA3
NM_000743.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.830

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000253 (38/149990) while in subpopulation SAS AF= 0.00568 (27/4752). AF 95% confidence interval is 0.00401. There are 1 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
CHRNA3	NM_000743.5 linkuse as main transcript	c.162_163del	3_prime_UTR_variant	6/6	ENST00000326828.6	NP_000734.2
CHRNA3	XM_006720382.4 linkuse as main transcript	c.162_163del	3_prime_UTR_variant	6/6		XP_006720445.1
CHRNA3	NM_001166694.2 linkuse as main transcript	c.1390-3251_1390-3250del	intron_variant			NP_001160166.1
CHRNA3	NR_046313.2 linkuse as main transcript	n.1784+98_1784+99del	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6 linkuse as main transcript	c.162_163del	3_prime_UTR_variant	6/6	1	NM_000743.5	ENSP00000315602	P1	P32297-2
CHRNA3	ENST00000348639.7 linkuse as main transcript	c.1390-3251_1390-3250del	intron_variant		1		ENSP00000267951		P32297-3
CHRNA3	ENST00000559002.5 linkuse as main transcript	n.193+98_193+99del	intron_variant, non_coding_transcript_variant		1
CHRNA3	ENST00000559658.5 linkuse as main transcript	c.64+98_64+99del	intron_variant, NMD_transcript_variant		2		ENSP00000452896		P32297-2

Frequencies

GnomAD3 genomes

AF:

0.000260

AC:

AN:

149884

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000664

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000583

Gnomad SAS

AF:

0.00588

Gnomad FIN

AF:

0.0000998

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00135

AC:

1308

AN:

970828

Hom.:

AF XY:

0.00147

AC XY:

677

AN XY:

462086

show subpopulations

Gnomad4 AFR exome

AF:

0.00211

Gnomad4 AMR exome

AF:

0.00727

Gnomad4 ASJ exome

AF:

0.00253

Gnomad4 EAS exome

AF:

0.0151

Gnomad4 SAS exome

AF:

0.00817

Gnomad4 FIN exome

AF:

0.00238

Gnomad4 NFE exome

AF:

0.000617

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.000253

AC:

AN:

149990

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

AN XY:

73200

show subpopulations

Gnomad4 AFR

AF:

0.000122

Gnomad4 AMR

AF:

0.0000663

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000584

Gnomad4 SAS

AF:

0.00568

Gnomad4 FIN

AF:

0.0000998

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over