rs10022491

chr4-40335891-T-Cchr4-40335891-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017581.4(CHRNA9):c.129T>C(p.Ser43=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,608,422 control chromosomes in the GnomAD database, including 264,161 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 0.65 (33428 hom., cov: 32)
  • Exomes 𝑓: 0.56 (230733 hom.)
• Consequence: CHRNA9 NM_017581.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA9	NM_017581.4	c.129T>C	p.Ser43=	synonymous_variant	2/5	ENST00000310169.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA9	ENST00000310169.3	c.129T>C	p.Ser43=	synonymous_variant	2/5	1	NM_017581.4	P1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98166 AN: 151952 Hom.: 33376 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.627

GnomAD3 exomes AF: 0.575 AC: 144236 AN: 250882 Hom.: 42718 AF XY: 0.566 AC XY: 76746 AN XY: 135598

Gnomad AFR exome AF: 0.880

Gnomad AMR exome AF: 0.640

Gnomad ASJ exome AF: 0.501

Gnomad EAS exome AF: 0.412

Gnomad SAS exome AF: 0.568

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.549

Gnomad OTH exome AF: 0.569

GnomAD4 exome AF: 0.559 AC: 814446 AN: 1456352 Hom.: 230733 Cov.: 31 AF XY: 0.558 AC XY: 404057 AN XY: 724734

Gnomad4 AFR exome AF: 0.885

Gnomad4 AMR exome AF: 0.635

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.560

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.646 AC: 98271 AN: 152070 Hom.: 33428 Cov.: 32 AF XY: 0.643 AC XY: 47809 AN XY: 74328

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.628

Alfa AF: 0.578 Hom.: 33620

Bravo AF: 0.660

Asia WGS AF: 0.525 AC: 1823 AN: 3478

EpiCase AF: 0.551

EpiControl AF: 0.543

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	13
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10022491; hg19: chr4-40337908; COSMIC: COSV59574605; COSMIC: COSV59574605;