rs4264869

Variant names:

• chr4-40353109-C-T
• rs4264869
• NM_017581.4:c.899-870C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.88).
• 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 rank	MANE	Protein	UniProt
CHRNA9	NM_017581.4	c.899-870C>T		intron_variant	Intron 4 of 4	ENST00000310169.3	NP_060051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3	c.899-870C>T		intron_variant	Intron 4 of 4	1	NM_017581.4	ENSP00000312663.2
CHRNA9	ENST00000509518.1	n.350-870C>T		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.282 AC: 11677 AN: 41388

American (AMR) AF: 0.462 AC: 7037 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1931 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4243 AN: 5174

South Asian (SAS) AF: 0.603 AC: 2891 AN: 4794

European-Finnish (FIN) AF: 0.537 AC: 5637 AN: 10502

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35047 AN: 67946

Other (OTH) AF: 0.491 AC: 1035 AN: 2106

Alfa AF: 0.462 Hom.: 3157

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
PhyloP100		-0.23
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: rs4264869; hg19: chr4-40355126;