rs60714708

Positions:

• chr4-40337046-C-T

Variant summary

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

The NM_017581.4(CHRNA9):​c.211-164C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,150 control chromosomes in the GnomAD database, including 1,862 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 0.088 (1862 hom., cov: 33)
• Consequence: CHRNA9 NM_017581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA9	NM_017581.4	c.211-164C>T		intron_variant		ENST00000310169.3	NP_060051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3	c.211-164C>T		intron_variant		1	NM_017581.4	ENSP00000312663.2

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13350 AN: 152032 Hom.: 1856 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0376

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.0660

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

GnomAD4 genome AF: 0.0879 AC: 13380 AN: 152150 Hom.: 1862 Cov.: 33 AF XY: 0.0851 AC XY: 6331 AN XY: 74392

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.0376

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0231

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00187

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0670 Hom.: 144

Bravo AF: 0.0992

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.41

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: rs60714708; hg19: chr4-40339063;