chr4-40337120-G-C

Position:

• chr4-40337120-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017581.4(CHRNA9):​c.211-90G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 1,204,770 control chromosomes in the GnomAD database, including 1,981 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 0.066 (485 hom., cov: 33)
  • Exomes 𝑓: 0.049 (1496 hom.)
• Consequence: CHRNA9 NM_017581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA9	NM_017581.4	c.211-90G>C		intron_variant		ENST00000310169.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA9	ENST00000310169.3	c.211-90G>C		intron_variant		1	NM_017581.4	P1

Frequencies

GnomAD3 genomes AF: 0.0656 AC: 9979 AN: 152196 Hom.: 485 Cov.: 33

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0364

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0622

GnomAD4 exome AF: 0.0492 AC: 51731 AN: 1052456 Hom.: 1496 AF XY: 0.0484 AC XY: 25554 AN XY: 528180

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.0310

Gnomad4 ASJ exome AF: 0.0698

Gnomad4 EAS exome AF: 0.000383

Gnomad4 SAS exome AF: 0.0355

Gnomad4 FIN exome AF: 0.0161

Gnomad4 NFE exome AF: 0.0521

Gnomad4 OTH exome AF: 0.0549

GnomAD4 genome AF: 0.0656 AC: 9986 AN: 152314 Hom.: 485 Cov.: 33 AF XY: 0.0633 AC XY: 4718 AN XY: 74482

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0431

Gnomad4 ASJ AF: 0.0689

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0360

Gnomad4 FIN AF: 0.0141

Gnomad4 NFE AF: 0.0522

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0575 Hom.: 43

Bravo AF: 0.0714

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs6447332; hg19: chr4-40339137;