NM_017581.4:c.365+5014T>C

Variant names:

• chr4-40342378-T-C
• rs4861065
• NM_017581.4:c.365+5014T>C

Variant summary

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

The NM_017581.4(CHRNA9):​c.365+5014T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,026 control chromosomes in the GnomAD database, including 8,181 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 0.32 (8181 hom., cov: 32)
• Consequence: CHRNA9 NM_017581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.905

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA9	NM_017581.4	c.365+5014T>C		intron_variant	Intron 3 of 4	ENST00000310169.3	NP_060051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3	c.365+5014T>C		intron_variant	Intron 3 of 4	1	NM_017581.4	ENSP00000312663.2
CHRNA9	ENST00000502377.1	n.269+4137T>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47997 AN: 151908 Hom.: 8176 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.316 AC: 48034 AN: 152026 Hom.: 8181 Cov.: 32 AF XY: 0.310 AC XY: 23027 AN XY: 74310

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.0522

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.300

Alfa AF: 0.296 Hom.: 9155

Bravo AF: 0.321

Asia WGS AF: 0.154 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.70

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: rs4861065; hg19: chr4-40344395;