15-78596749-TAAAA-T

Position:

• chr15-78596749-TAAAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.401

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]

ACMG classification

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
CHRNA3	NM_000743.5	c.1390-21_1390-18del		intron_variant		ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.1390-3562_1390-3559del		intron_variant			NP_001160166.1
CHRNA3	XM_006720382.4	c.1189-21_1189-18del		intron_variant			XP_006720445.1
CHRNA3	NR_046313.2	n.1592-21_1592-18del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.1390-21_1390-18del		intron_variant		1	NM_000743.5	ENSP00000315602	P1
CHRNA3	ENST00000348639.7	c.1390-3562_1390-3559del		intron_variant		1		ENSP00000267951
CHRNA3	ENST00000559658.5	c.1390-21_1390-18del		intron_variant, NMD_transcript_variant		2		ENSP00000452896
CHRNA3	ENST00000559002.5			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 382 AN: 151878 Hom.: 1 Cov.: 32

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

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

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

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: rs149274426; hg19: chr15-78889091;