chr15-78596749-TAAAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000743.5(CHRNA3):​c.1390-21_1390-18del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000464 in 1,584,712 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 4 hom. )

Consequence

CHRNA3
NM_000743.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.401
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 15-78596749-TAAAA-T is Benign according to our data. Variant chr15-78596749-TAAAA-T is described in ClinVar as [Benign]. Clinvar id is 1971188.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00251 (381/151996) while in subpopulation AFR AF= 0.00875 (363/41484). AF 95% confidence interval is 0.00801. There are 1 homozygotes in gnomad4. There are 182 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CHRNA3NM_000743.5 linkuse as main transcriptc.1390-21_1390-18del intron_variant ENST00000326828.6 NP_000734.2
CHRNA3NM_001166694.2 linkuse as main transcriptc.1390-3562_1390-3559del intron_variant NP_001160166.1
CHRNA3XM_006720382.4 linkuse as main transcriptc.1189-21_1189-18del intron_variant XP_006720445.1
CHRNA3NR_046313.2 linkuse as main transcriptn.1592-21_1592-18del intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHRNA3ENST00000326828.6 linkuse as main transcriptc.1390-21_1390-18del intron_variant 1 NM_000743.5 ENSP00000315602 P1P32297-2
CHRNA3ENST00000348639.7 linkuse as main transcriptc.1390-3562_1390-3559del intron_variant 1 ENSP00000267951 P32297-3
CHRNA3ENST00000559658.5 linkuse as main transcriptc.1390-21_1390-18del intron_variant, NMD_transcript_variant 2 ENSP00000452896 P32297-2
CHRNA3ENST00000559002.5 linkuse as main transcript upstream_gene_variant 1

Frequencies

GnomAD3 genomes
AF:
0.00252
AC:
382
AN:
151878
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00878
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000721
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000589
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000740
AC:
163
AN:
220344
Hom.:
2
AF XY:
0.000591
AC XY:
71
AN XY:
120218
show subpopulations
Gnomad AFR exome
AF:
0.00995
Gnomad AMR exome
AF:
0.000230
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000408
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000384
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000248
AC:
355
AN:
1432716
Hom.:
4
AF XY:
0.000223
AC XY:
159
AN XY:
712588
show subpopulations
Gnomad4 AFR exome
AF:
0.0101
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000248
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000634
Gnomad4 OTH exome
AF:
0.000339
GnomAD4 genome
AF:
0.00251
AC:
381
AN:
151996
Hom.:
1
Cov.:
32
AF XY:
0.00245
AC XY:
182
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.00875
Gnomad4 AMR
AF:
0.000720
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000589
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.00113
Hom.:
0
Bravo
AF:
0.00251

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 23, 2023- -

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.

Other links and lift over

dbSNP: rs149274426; hg19: chr15-78889091; API