rs4264869

chr4-40353109-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.899-870C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,826 control chromosomes in the GnomAD database, including 17,301 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 0.46 (17301 hom., cov: 32)
• Consequence: CHRNA9 NM_017581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA9	NM_017581.4	c.899-870C>T		intron_variant		ENST00000310169.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA9	ENST00000310169.3	c.899-870C>T		intron_variant		1	NM_017581.4	P1
CHRNA9	ENST00000509518.1	n.350-870C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70004 AN: 151708 Hom.: 17291 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.461 AC: 70042 AN: 151826 Hom.: 17301 Cov.: 32 AF XY: 0.466 AC XY: 34550 AN XY: 74162

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.491

Alfa AF: 0.468 Hom.: 3119

Bravo AF: 0.449

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.3
Dann	Benign	0.38

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: rs4264869; hg19: chr4-40355126;