4-40337026-GA-GAA

Variant names:

• chr4-40337026-G-GA
• rs182073550
• NM_017581.4:c.211-176dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_017581.4(CHRNA9):​c.211-176dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0685 in 151,742 control chromosomes in the GnomAD database, including 445 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.068 (445 hom., cov: 31)
• Consequence: CHRNA9 NM_017581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017581.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA9	NM_017581.4	MANE Select	c.211-176dupA		intron	N/A	NP_060051.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA9	ENST00000310169.3	TSL:1 MANE Select	c.211-176dupA		intron	N/A	ENSP00000312663.2

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10381 AN: 151626 Hom.: 444 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.0551

Gnomad SAS AF: 0.0264

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.0605

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

GnomAD4 genome AF: 0.0685 AC: 10391 AN: 151742 Hom.: 445 Cov.: 31 AF XY: 0.0687 AC XY: 5093 AN XY: 74142

African (AFR) AF: 0.117 AC: 4838 AN: 41374

American (AMR) AF: 0.0530 AC: 808 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 267 AN: 3460

East Asian (EAS) AF: 0.0551 AC: 284 AN: 5158

South Asian (SAS) AF: 0.0260 AC: 125 AN: 4812

European-Finnish (FIN) AF: 0.0925 AC: 968 AN: 10470

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0432 AC: 2932 AN: 67910

Other (OTH) AF: 0.0598 AC: 126 AN: 2106

Alfa AF: 0.0177 Hom.: 10

Bravo AF: 0.0693

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.040
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs182073550; hg19: chr4-40339043;