chr4-40354882-C-T

Variant names:

• chr4-40354882-C-T
• rs56291234
• NM_017581.4:c.*362C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017581.4(CHRNA9):​c.*362C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 179,834 control chromosomes in the GnomAD database, including 1,424 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 0.099 (1375 hom., cov: 32)
  • Exomes 𝑓: 0.044 (49 hom.)
• Consequence: CHRNA9 NM_017581.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA9	NM_017581.4	MANE Select	c.*362C>T		3_prime_UTR	Exon 5 of 5	NP_060051.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA9	ENST00000310169.3	TSL:1 MANE Select	c.*362C>T		3_prime_UTR	Exon 5 of 5	ENSP00000312663.2

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15013 AN: 152036 Hom.: 1371 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0876

GnomAD4 exome AF: 0.0444 AC: 1230 AN: 27680 Hom.: 49 Cov.: 0 AF XY: 0.0442 AC XY: 635 AN XY: 14378

African (AFR) AF: 0.179 AC: 139 AN: 778

American (AMR) AF: 0.0421 AC: 142 AN: 3374

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 65 AN: 664

East Asian (EAS) AF: 0.00 AC: 0 AN: 2042

South Asian (SAS) AF: 0.0390 AC: 104 AN: 2670

European-Finnish (FIN) AF: 0.0179 AC: 15 AN: 840

Middle Eastern (MID) AF: 0.0541 AC: 4 AN: 74

European-Non Finnish (NFE) AF: 0.0436 AC: 691 AN: 15848

Other (OTH) AF: 0.0504 AC: 70 AN: 1390

GnomAD4 genome AF: 0.0989 AC: 15041 AN: 152154 Hom.: 1375 Cov.: 32 AF XY: 0.0957 AC XY: 7121 AN XY: 74404

African (AFR) AF: 0.234 AC: 9695 AN: 41478

American (AMR) AF: 0.0544 AC: 832 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.0354 AC: 171 AN: 4826

European-Finnish (FIN) AF: 0.0140 AC: 148 AN: 10606

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0522 AC: 3550 AN: 67988

Other (OTH) AF: 0.0866 AC: 183 AN: 2112

Alfa AF: 0.0679 Hom.: 558

Bravo AF: 0.109

Asia WGS AF: 0.0370 AC: 128 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.24
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs56291234; hg19: chr4-40356899;