rs10015231

Positions:

• chr4-40335549-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.64+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,589,974 control chromosomes in the GnomAD database, including 40,307 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 0.21 (3715 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36592 hom.)
• Consequence: CHRNA9 NM_017581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA9	NM_017581.4	c.64+18C>T		intron_variant		ENST00000310169.3	NP_060051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3	c.64+18C>T		intron_variant		1	NM_017581.4	ENSP00000312663.2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32431 AN: 152076 Hom.: 3718 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.219

GnomAD3 exomes AF: 0.235 AC: 59087 AN: 251016 Hom.: 7583 AF XY: 0.233 AC XY: 31544 AN XY: 135662

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.365

Gnomad ASJ exome AF: 0.221

Gnomad EAS exome AF: 0.144

Gnomad SAS exome AF: 0.203

Gnomad FIN exome AF: 0.300

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.232

GnomAD4 exome AF: 0.222 AC: 319329 AN: 1437780 Hom.: 36592 Cov.: 28 AF XY: 0.222 AC XY: 159173 AN XY: 717054

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.356

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.213 AC: 32438 AN: 152194 Hom.: 3715 Cov.: 32 AF XY: 0.216 AC XY: 16065 AN XY: 74392

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.217

Alfa AF: 0.216 Hom.: 2017

Bravo AF: 0.212

Asia WGS AF: 0.163 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.65

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: rs10015231; hg19: chr4-40337566; COSMIC: COSV59574594; COSMIC: COSV59574594;