rs55974552

Variant names:

• chr4-40335951-G-A
• rs55974552
• NM_017581.4:c.189G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_017581.4(CHRNA9):​c.189G>A​(p.Thr63Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,612,528 control chromosomes in the GnomAD database, including 197 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 0.013 (21 hom., cov: 32)
  • Exomes 𝑓: 0.014 (176 hom.)
• Consequence: CHRNA9 NM_017581.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 5 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-1.8 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.013 (1975/152274) while in subpopulation AMR AF = 0.0247 (378/15292). AF 95% confidence interval is 0.0227. There are 21 homozygotes in GnomAd4. There are 971 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

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.189G>A	p.Thr63Thr	synonymous	Exon 2 of 5	NP_060051.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA9	ENST00000310169.3	TSL:1 MANE Select	c.189G>A	p.Thr63Thr	synonymous	Exon 2 of 5	ENSP00000312663.2

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1977 AN: 152156 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00314

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0335

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00773

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0206

GnomAD2 exomes AF: 0.0136 AC: 3422 AN: 251266 AF XY: 0.0145

Gnomad AFR exome AF: 0.00271

Gnomad AMR exome AF: 0.0156

Gnomad ASJ exome AF: 0.0298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00722

Gnomad NFE exome AF: 0.0179

Gnomad OTH exome AF: 0.0170

GnomAD4 exome AF: 0.0141 AC: 20618 AN: 1460254 Hom.: 176 Cov.: 30 AF XY: 0.0143 AC XY: 10387 AN XY: 726524

African (AFR) AF: 0.00397 AC: 133 AN: 33474

American (AMR) AF: 0.0164 AC: 731 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0305 AC: 798 AN: 26128

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39696

South Asian (SAS) AF: 0.00808 AC: 697 AN: 86214

European-Finnish (FIN) AF: 0.00876 AC: 468 AN: 53404

Middle Eastern (MID) AF: 0.0536 AC: 309 AN: 5760

European-Non Finnish (NFE) AF: 0.0148 AC: 16476 AN: 1110528

Other (OTH) AF: 0.0166 AC: 1001 AN: 60342

GnomAD4 genome AF: 0.0130 AC: 1975 AN: 152274 Hom.: 21 Cov.: 32 AF XY: 0.0130 AC XY: 971 AN XY: 74460

African (AFR) AF: 0.00313 AC: 130 AN: 41554

American (AMR) AF: 0.0247 AC: 378 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0335 AC: 116 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00643 AC: 31 AN: 4824

European-Finnish (FIN) AF: 0.00773 AC: 82 AN: 10608

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0172 AC: 1168 AN: 68030

Other (OTH) AF: 0.0203 AC: 43 AN: 2114

Alfa AF: 0.0145 Hom.: 14

Bravo AF: 0.0143

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0212

EpiControl AF: 0.0235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.93
DANN	Benign	0.70
PhyloP100		-1.8
Mutation Taster		=100/0	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: rs55974552; hg19: chr4-40337968;