4-40354697-A-T

Position:

• chr4-40354697-A-T

Variant summary

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

The ENST00000310169.3(CHRNA9):​c.*177A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 590,168 control chromosomes in the GnomAD database, including 258,424 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 0.92 (64288 hom., cov: 31)
  • Exomes 𝑓: 0.94 (194136 hom.)
• Consequence: CHRNA9 ENST00000310169.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

Genes affected

CHRNA9 (HGNC:14079): (cholinergic receptor nicotinic alpha 9 subunit) This gene is a member of the ligand-gated ionic channel family and nicotinic acetylcholine receptor gene superfamily. It encodes a plasma membrane protein that forms homo- or hetero-oligomeric divalent cation channels. This protein is involved in cochlea hair cell development and is also expressed in the outer hair cells (OHCs) of the adult cochlea. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA9	NM_017581.4	c.*177A>T		3_prime_UTR_variant	5/5	ENST00000310169.3	NP_060051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3	c.*177A>T		3_prime_UTR_variant	5/5	1	NM_017581.4	ENSP00000312663	P1

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139599 AN: 152100 Hom.: 64253 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.922

GnomAD4 exome AF: 0.941 AC: 412002 AN: 437950 Hom.: 194136 Cov.: 5 AF XY: 0.941 AC XY: 214955 AN XY: 228396

Gnomad4 AFR exome AF: 0.872

Gnomad4 AMR exome AF: 0.802

Gnomad4 ASJ exome AF: 0.931

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.946

Gnomad4 FIN exome AF: 0.969

Gnomad4 NFE exome AF: 0.944

Gnomad4 OTH exome AF: 0.937

GnomAD4 genome AF: 0.918 AC: 139688 AN: 152218 Hom.: 64288 Cov.: 31 AF XY: 0.916 AC XY: 68160 AN XY: 74426

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.925

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.955

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.946

Gnomad4 OTH AF: 0.923

Alfa AF: 0.931 Hom.: 8291

Bravo AF: 0.906

Asia WGS AF: 0.973 AC: 3382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.47

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: rs4861327; hg19: chr4-40356714;