Variant chrX-151738527-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005140.3(CNGA2):c.44A>C(p.Asn15Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,209,940 control chromosomes in the GnomAD database, including 11 homozygotes. There are 384 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 5 hom., 177 hem., cov: 22)

Exomes 𝑓: 0.00070 ( 6 hom. 207 hem. )

Consequence

CNGA2
NM_005140.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.08

Variant links:

Genes affected

CNGA2 (HGNC:2149): (cyclic nucleotide gated channel subunit alpha 2) The protein encoded by this gene represents the alpha subunit of a cyclic nucleotide-gated olfactory channel. The encoded protein contains a carboxy-terminal leucine zipper that mediates channel formation. [provided by RefSeq, Jan 2010]

CNGA2 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=0.0050972104).

BP6

Variant X-151738527-A-C is Benign according to our data. Variant chrX-151738527-A-C is described in ClinVar as [Benign]. Clinvar id is 784435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-151738527-A-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00654 (732/111845) while in subpopulation AFR AF= 0.0225 (693/30762). AF 95% confidence interval is 0.0211. There are 5 homozygotes in gnomad4. There are 177 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGA2	NM_005140.3 link	c.44A>C	p.Asn15Thr	missense_variant	2/7	ENST00000329903.5	NP_005131.1	Q16280B3KXY3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGA2	ENST00000329903.5 link	c.44A>C	p.Asn15Thr	missense_variant	2/7	5	NM_005140.3	ENSP00000328478.4		Q16280

Frequencies

GnomAD3 genomes

AF:

0.00651

AC:

728

AN:

111794

Hom.:

Cov.:

AF XY:

0.00518

AC XY:

176

AN XY:

33966

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00183

AC:

335

AN:

183290

Hom.:

AF XY:

0.00114

AC XY:

AN XY:

67742

show subpopulations

Gnomad AFR exome

AF:

0.0213

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000157

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000856

Gnomad OTH exome

AF:

0.000884

GnomAD4 exome

AF:

0.000698

AC:

766

AN:

1098095

Hom.:

Cov.:

AF XY:

0.000570

AC XY:

207

AN XY:

363455

show subpopulations

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.00162

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000321

Gnomad4 OTH exome

AF:

0.00178

GnomAD4 genome

AF:

0.00654

AC:

732

AN:

111845

Hom.:

Cov.:

AF XY:

0.00520

AC XY:

177

AN XY:

34027

show subpopulations

Gnomad4 AFR

AF:

0.0225

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.00329

Alfa

AF:

0.000282

Hom.:

Bravo

AF:

0.00780

ESP6500AA

AF:

0.0232

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00214

AC:

260

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

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	Apr 23, 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

0.075

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.075

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0051

MetaSVM

Uncertain

0.20

MutationAssessor

Benign

-0.69

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.47

REVEL

Benign

0.28

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.98

Vest4

0.10

MVP

0.89

MPC

0.067

ClinPred

0.035

GERP RS

3.7

Varity_R

0.071

gMVP

0.30

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