rs529317428

Variant names:

• chr4-40335523-G-C
• rs529317428
• NM_017581.4:c.56G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-40335523-G-C
• chr4-40335523-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017581.4(CHRNA9):​c.56G>C​(p.Arg19Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CHRNA9 NM_017581.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15239334).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017581.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA9	NM_017581.4	MANE Select	c.56G>C	p.Arg19Thr	missense	Exon 1 of 5	NP_060051.2	Q9UGM1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA9	ENST00000310169.3	TSL:1 MANE Select	c.56G>C	p.Arg19Thr	missense	Exon 1 of 5	ENSP00000312663.2	Q9UGM1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251424 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460144 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726580

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110396

Other (OTH) AF: 0.0000497 AC: 3 AN: 60350

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152352 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74514

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.000654 AC: 10 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000147

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.9
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.64	N
REVEL	Uncertain	0.36
Sift	Benign	0.42	T
Sift4G	Benign	0.39	T
Polyphen		0.023	B
Vest4		0.52
MutPred		0.56		Loss of methylation at R19 (P = 0.0337)
MVP		0.63
MPC		0.096
ClinPred		0.21	T
GERP RS		4.5
PromoterAI		-0.043	Neutral
Varity_R		0.054
gMVP		0.60
Mutation Taster		=79/21	polymorphism

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: rs529317428; hg19: chr4-40337540;