Genetic Variant CHRNA3:c.1390-21_1390-18delTTTT (chr15-78596749-TAAAA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000743.5(CHRNA3):c.1390-21_1390-18delTTTT 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]

CHRNA3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5 link	c.1390-21_1390-18delTTTT	intron_variant	Intron 5 of 5	ENST00000326828.6	NP_000734.2	P32297-2
CHRNA3	NM_001166694.2 link	c.1390-3562_1390-3559delTTTT	intron_variant	Intron 5 of 5		NP_001160166.1	P32297-3
CHRNA3	XM_006720382.4 link	c.1189-21_1189-18delTTTT	intron_variant	Intron 5 of 5		XP_006720445.1
CHRNA3	NR_046313.2 link	n.1592-21_1592-18delTTTT	intron_variant	Intron 5 of 7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRNA3	ENST00000326828.6 link	c.1390-21_1390-18delTTTT	intron_variant	Intron 5 of 5	1	NM_000743.5	ENSP00000315602.5	P32297-2
CHRNA3	ENST00000348639.7 link	c.1390-3562_1390-3559delTTTT	intron_variant	Intron 5 of 5	1		ENSP00000267951.4	P32297-3
CHRNA3	ENST00000559658.5 link	n.1390-21_1390-18delTTTT	intron_variant	Intron 5 of 7	2		ENSP00000452896.1	P32297-2
CHRNA3	ENST00000559002.5 link	n.-21_-18delTTTT	upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

382

AN:

151878

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000740

AC:

163

AN:

220344

AF XY:

0.000591

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 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.:

AF XY:

0.000223

AC XY:

159

AN XY:

712588

show subpopulations

Gnomad4 AFR exome

AF:

0.0101

AC:

317

AN:

31500

Gnomad4 AMR exome

AF:

0.000224

AC:

AN:

35710

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

24908

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39112

Gnomad4 SAS exome

AF:

0.0000248

AC:

AN:

80638

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

52450

Gnomad4 NFE exome

AF:

0.00000634

AC:

AN:

1103754

Gnomad4 Remaining exome

AF:

0.000339

AC:

AN:

59032

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00251

AC:

381

AN:

151996

Hom.:

Cov.:

AF XY:

0.00245

AC XY:

182

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00875

AC:

0.00875036

AN:

0.00875036

Gnomad4 AMR

AF:

0.000720

AC:

0.000720461

AN:

0.000720461

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000589

AC:

0.0000588668

AN:

0.0000588668

Gnomad4 OTH

AF:

0.000947

AC:

0.00094697

AN:

0.00094697

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00113

Hom.:

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

Dec 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over