4-40337233-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017581.4(CHRNA9):c.234T>C(p.Thr78=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00754 in 1,614,194 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0077 (56 hom.)
• Consequence: CHRNA9 NM_017581.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.90

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-40337233-T-C is Benign according to our data. Variant chr4-40337233-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2654735.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00772 (11281/1461836) while in subpopulation MID AF= 0.018 (104/5768). AF 95% confidence interval is 0.0152. There are 56 homozygotes in gnomad4_exome. There are 5669 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA9	NM_017581.4	c.234T>C	p.Thr78=	synonymous_variant	3/5	ENST00000310169.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA9	ENST00000310169.3	c.234T>C	p.Thr78=	synonymous_variant	3/5	1	NM_017581.4	P1

Frequencies

GnomAD3 genomes AF: 0.00587 AC: 894 AN: 152240 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.00537

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00932

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00640 AC: 1608 AN: 251366 Hom.: 3 AF XY: 0.00647 AC XY: 879 AN XY: 135858

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.00903

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00497

Gnomad FIN exome AF: 0.00684

Gnomad NFE exome AF: 0.00874

Gnomad OTH exome AF: 0.00766

GnomAD4 exome AF: 0.00772 AC: 11281 AN: 1461836 Hom.: 56 Cov.: 31 AF XY: 0.00780 AC XY: 5669 AN XY: 727214

Gnomad4 AFR exome AF: 0.00140

Gnomad4 AMR exome AF: 0.00445

Gnomad4 ASJ exome AF: 0.00930

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00497

Gnomad4 FIN exome AF: 0.00711

Gnomad4 NFE exome AF: 0.00844

Gnomad4 OTH exome AF: 0.00823

GnomAD4 genome AF: 0.00586 AC: 893 AN: 152358 Hom.: 4 Cov.: 33 AF XY: 0.00573 AC XY: 427 AN XY: 74516

Gnomad4 AFR AF: 0.00144

Gnomad4 AMR AF: 0.00470

Gnomad4 ASJ AF: 0.00807

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00642

Gnomad4 FIN AF: 0.00537

Gnomad4 NFE AF: 0.00932

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00746 Hom.: 4

Bravo AF: 0.00516

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00943

EpiControl AF: 0.0102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

CHRNA9: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.13
Dann	Benign	0.38

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: rs55998310; hg19: chr4-40339250;