chr4-40347325-G-C

Position:

• chr4-40347325-G-C

Variant summary

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

The NM_017581.4(CHRNA9):​c.366-1557G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,086 control chromosomes in the GnomAD database, including 2,794 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 0.17 (2794 hom., cov: 32)
• Consequence: CHRNA9 NM_017581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA9	NM_017581.4	c.366-1557G>C		intron_variant		ENST00000310169.3	NP_060051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3	c.366-1557G>C		intron_variant		1	NM_017581.4	ENSP00000312663	P1
CHRNA9	ENST00000502377.1	n.270-462G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25732 AN: 151968 Hom.: 2796 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0482

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25730 AN: 152086 Hom.: 2794 Cov.: 32 AF XY: 0.169 AC XY: 12528 AN XY: 74330

Gnomad4 AFR AF: 0.0441

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.0485

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.175

Alfa AF: 0.0917 Hom.: 183

Bravo AF: 0.158

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.78

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: rs6819483; hg19: chr4-40349342;