4-40354697-A-T

Variant names:

• chr4-40354697-A-T
• rs4861327
• NM_017581.4:c.*177A>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.*177A>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 0.935 in 590,168 control chromosomes in the GnomAD database, including 258,424 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 0.92 (64288 hom., cov: 31)
  • Exomes 𝑓: 0.94 (194136 hom.)
• Consequence: CHRNA9 NM_017581.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.*177A>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.*177A>T		3_prime_UTR	Exon 5 of 5	ENSP00000312663.2

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139599 AN: 152100 Hom.: 64253 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.922

GnomAD4 exome AF: 0.941 AC: 412002 AN: 437950 Hom.: 194136 Cov.: 5 AF XY: 0.941 AC XY: 214955 AN XY: 228396

African (AFR) AF: 0.872 AC: 10974 AN: 12582

American (AMR) AF: 0.802 AC: 13797 AN: 17198

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 12053 AN: 12942

East Asian (EAS) AF: 1.00 AC: 30025 AN: 30036

South Asian (SAS) AF: 0.946 AC: 33494 AN: 35388

European-Finnish (FIN) AF: 0.969 AC: 26540 AN: 27386

Middle Eastern (MID) AF: 0.898 AC: 1679 AN: 1870

European-Non Finnish (NFE) AF: 0.944 AC: 260024 AN: 275568

Other (OTH) AF: 0.937 AC: 23416 AN: 24980

GnomAD4 genome AF: 0.918 AC: 139688 AN: 152218 Hom.: 64288 Cov.: 31 AF XY: 0.916 AC XY: 68160 AN XY: 74426

African (AFR) AF: 0.875 AC: 36316 AN: 41504

American (AMR) AF: 0.826 AC: 12613 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3209 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5189 AN: 5196

South Asian (SAS) AF: 0.955 AC: 4606 AN: 4822

European-Finnish (FIN) AF: 0.972 AC: 10306 AN: 10604

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.946 AC: 64337 AN: 68034

Other (OTH) AF: 0.923 AC: 1954 AN: 2116

Alfa AF: 0.931 Hom.: 8291

Bravo AF: 0.906

Asia WGS AF: 0.973 AC: 3382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.47
PhyloP100		-0.20
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: rs4861327; hg19: chr4-40356714;