Variant rs55998310 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.90

Variant links:

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]

CHRNA9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA9	NM_017581.4 linkuse as main transcript	c.234T>C	p.Thr78=	synonymous_variant	3/5	ENST00000310169.3	NP_060051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3 linkuse as main transcript	c.234T>C	p.Thr78=	synonymous_variant	3/5	1	NM_017581.4	ENSP00000312663	P1

Frequencies

GnomAD3 genomes

AF:

0.00587

AC:

894

AN:

152240

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00647

AC XY:

879

AN XY:

135858

show subpopulations

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.:

Cov.:

AF XY:

0.00780

AC XY:

5669

AN XY:

727214

show subpopulations

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.:

Cov.:

AF XY:

0.00573

AC XY:

427

AN XY:

74516

show subpopulations

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.:

Bravo

AF:

0.00516

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00943

EpiControl

AF:

0.0102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over