15-78596749-TAAAAG-T

Position:

• chr15-78596749-TAAAAG-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_000743.5(CHRNA3):​c.1390-22_1390-18del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,584,714 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Likely 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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 15-78596749-TAAAAG-T is Benign according to our data. Variant chr15-78596749-TAAAAG-T is described in ClinVar as [Likely_benign]. Clinvar id is 2023242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000197 (30/151996) while in subpopulation AFR AF= 0.000627 (26/41484). AF 95% confidence interval is 0.000439. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.1390-22_1390-18del		intron_variant		ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.1390-3563_1390-3559del		intron_variant			NP_001160166.1
CHRNA3	XM_006720382.4	c.1189-22_1189-18del		intron_variant			XP_006720445.1
CHRNA3	NR_046313.2	n.1592-22_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.1390-22_1390-18del		intron_variant		1	NM_000743.5	ENSP00000315602	P1
CHRNA3	ENST00000348639.7	c.1390-3563_1390-3559del		intron_variant		1		ENSP00000267951
CHRNA3	ENST00000559658.5	c.1390-22_1390-18del		intron_variant, NMD_transcript_variant		2		ENSP00000452896
CHRNA3	ENST00000559002.5			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 151878 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000363 AC: 8 AN: 220344 Hom.: 0 AF XY: 0.00000832 AC XY: 1 AN XY: 120218

Gnomad AFR exome AF: 0.000523

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000202 AC: 29 AN: 1432718 Hom.: 0 AF XY: 0.0000154 AC XY: 11 AN XY: 712590

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.0000372

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000634

Gnomad4 OTH exome AF: 0.0000339

GnomAD4 genome AF: 0.000197 AC: 30 AN: 151996 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74286

Gnomad4 AFR AF: 0.000627

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000170

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 26, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs755674938; hg19: chr15-78889091;