rs6819385

Variant names:

• chr4-40337557-A-G
• rs6819385
• NM_017581.4:c.365+193A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017581.4(CHRNA9):​c.365+193A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,120 control chromosomes in the GnomAD database, including 20,607 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 0.51 (20607 hom., cov: 33)
• Consequence: CHRNA9 NM_017581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 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.365+193A>G		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.365+193A>G		intron	N/A	ENSP00000312663.2
	CHRNA9	ENST00000502377.1	TSL:3	n.79+193A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77976 AN: 152002 Hom.: 20597 Cov.: 33

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.513 AC: 78033 AN: 152120 Hom.: 20607 Cov.: 33 AF XY: 0.510 AC XY: 37910 AN XY: 74346

African (AFR) AF: 0.627 AC: 26021 AN: 41488

American (AMR) AF: 0.533 AC: 8149 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1495 AN: 3472

East Asian (EAS) AF: 0.179 AC: 927 AN: 5184

South Asian (SAS) AF: 0.399 AC: 1927 AN: 4826

European-Finnish (FIN) AF: 0.497 AC: 5247 AN: 10550

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32566 AN: 67992

Other (OTH) AF: 0.495 AC: 1046 AN: 2112

Alfa AF: 0.509 Hom.: 3382

Bravo AF: 0.519

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.81
PhyloP100		-0.42
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: rs6819385; hg19: chr4-40339574;