Variant 11-6240263-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001037329.4(CNGA4):c.469A>G(p.Thr157Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00805 in 1,614,204 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 91 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 102 hom. )

Consequence

CNGA4
NM_001037329.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.43

Variant links:

Genes affected

CNGA4 (HGNC:2152): (cyclic nucleotide gated channel subunit alpha 4) CNGA4 is a modulatory subunit of vertebrate cyclic nucleotide-gated membrane channels that transduce odorant signals (Munger et al., 2001 [PubMed 11739959]).[supplied by OMIM, Mar 2008]

CNGA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005527973).

BP6

Variant 11-6240263-A-G is Benign according to our data. Variant chr11-6240263-A-G is described in ClinVar as [Benign]. Clinvar id is 790360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGA4	NM_001037329.4 linkuse as main transcript	c.469A>G	p.Thr157Ala	missense_variant	4/6	ENST00000379936.3	NP_001032406.1	Q8IV77-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGA4	ENST00000379936.3 linkuse as main transcript	c.469A>G	p.Thr157Ala	missense_variant	4/6	1	NM_001037329.4	ENSP00000369268.2		Q8IV77-1
CNGA4	ENST00000533426.5 linkuse as main transcript	c.152-376A>G		intron_variant		2		ENSP00000433399.1		B4DYQ8

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3245

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0611

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0153

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00591

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.00810

AC:

2030

AN:

250722

Hom.:

AF XY:

0.00695

AC XY:

944

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.0649

Gnomad AMR exome

AF:

0.00766

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00171

Gnomad NFE exome

AF:

0.00553

Gnomad OTH exome

AF:

0.00556

GnomAD4 exome

AF:

0.00666

AC:

9741

AN:

1461854

Hom.:

102

Cov.:

AF XY:

0.00625

AC XY:

4546

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0624

Gnomad4 AMR exome

AF:

0.00859

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00230

Gnomad4 NFE exome

AF:

0.00585

Gnomad4 OTH exome

AF:

0.00881

GnomAD4 genome

AF:

0.0213

AC:

3247

AN:

152350

Hom.:

Cov.:

AF XY:

0.0209

AC XY:

1556

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0610

Gnomad4 AMR

AF:

0.0153

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00591

Gnomad4 OTH

AF:

0.0217

Alfa

AF:

0.00553

Hom.:

Bravo

AF:

0.0240

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.0591

AC:

260

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00920

AC:

1117

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00458

EpiControl

AF:

0.00569

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.72

Eigen

Benign

-0.070

Eigen_PC

Benign

-0.033

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0055

MetaSVM

Uncertain

0.25

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.47

Sift

Benign

0.034

Sift4G

Benign

0.070

Polyphen

0.14

Vest4

0.28

MVP

0.85

MPC

0.24

ClinPred

0.033

GERP RS

5.3

Varity_R

0.25

gMVP

0.64

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