rs4809549

Positions:

• chr20-63370757-G-C
• chr20-63370757-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000475033.5(CHRNA4):​n.3656C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,876 control chromosomes in the GnomAD database, including 15,926 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (15924 hom., cov: 31)
  • Exomes 𝑓: 0.40 (2 hom.)
• Consequence: CHRNA4 ENST00000475033.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

Genes affected

CHRNA4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC100130587	NR_110634.1	n.2948-104G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA4	ENST00000463705.5	n.1031+3124C>G		intron_variant		1
CHRNA4	ENST00000475033.5	n.3656C>G		non_coding_transcript_exon_variant	4/4	2
ENSG00000203900	ENST00000370257.1	n.2948-104G>C		intron_variant		2
ENSG00000203900	ENST00000428531.1	n.325+185G>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68760 AN: 151738 Hom.: 15924 Cov.: 31

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.400 AC: 8 AN: 20 Hom.: 2 Cov.: 0 AF XY: 0.400 AC XY: 4 AN XY: 10

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.453 AC: 68773 AN: 151856 Hom.: 15924 Cov.: 31 AF XY: 0.451 AC XY: 33484 AN XY: 74198

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.455

Alfa AF: 0.346 Hom.: 920

Bravo AF: 0.457

Asia WGS AF: 0.435 AC: 1512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4809549; hg19: chr20-62002109; COSMIC: COSV64718181;