rs6819385

chr4-40337557-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA9	NM_017581.4	c.365+193A>G		intron_variant		ENST00000310169.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA9	ENST00000310169.3	c.365+193A>G		intron_variant		1	NM_017581.4	P1
CHRNA9	ENST00000502377.1	n.79+193A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.495

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.6
Dann	Benign	0.81

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: rs6819385; hg19: chr4-40339574;