chr16-87888240-T-A

Position:

chr16-87888240-T-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001739.2(CA5A):c.807A>T(p.Ala269=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,613,382 control chromosomes in the GnomAD database, including 31,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2453 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29484 hom. )

Consequence

CA5A
NM_001739.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.78

Variant links:

Genes affected

CA5A (HGNC:1377): (carbonic anhydrase 5A) Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. CA VA is localized in the mitochondria and expressed primarily in the liver. It may play an important role in ureagenesis and gluconeogenesis. CA5A gene maps to chromosome 16q24.3 and an unprocessed pseudogene has been assigned to 16p12-p11.2. [provided by RefSeq, Jul 2008]

CA5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-87888240-T-A is Benign according to our data. Variant chr16-87888240-T-A is described in ClinVar as [Benign]. Clinvar id is 379955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-87888240-T-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.78 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CA5A	NM_001739.2 linkuse as main transcript	c.807A>T	p.Ala269=	synonymous_variant	7/7	ENST00000649794.3	NP_001730.1
CA5A	NM_001367225.1 linkuse as main transcript	c.774+3559A>T		intron_variant			NP_001354154.1
CA5A	NR_159798.1 linkuse as main transcript	n.994A>T		non_coding_transcript_exon_variant	8/8
CA5A	NR_159799.1 linkuse as main transcript	n.767A>T		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA5A	ENST00000649794.3 linkuse as main transcript	c.807A>T	p.Ala269=	synonymous_variant	7/7		NM_001739.2	ENSP00000498065	P1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26391

AN:

151892

Hom.:

2449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.183

AC:

45841

AN:

250754

Hom.:

4598

AF XY:

0.190

AC XY:

25736

AN XY:

135506

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.264

Gnomad EAS exome

AF:

0.142

Gnomad SAS exome

AF:

0.263

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.193

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.198

AC:

288821

AN:

1461372

Hom.:

29484

Cov.:

AF XY:

0.201

AC XY:

145884

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.137

Gnomad4 AMR exome

AF:

0.119

Gnomad4 ASJ exome

AF:

0.261

Gnomad4 EAS exome

AF:

0.134

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.174

AC:

26404

AN:

152010

Hom.:

2453

Cov.:

AF XY:

0.172

AC XY:

12803

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.272

Gnomad4 EAS

AF:

0.149

Gnomad4 SAS

AF:

0.270

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.199

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.122

Hom.:

316

Bravo

AF:

0.169

Asia WGS

AF:

0.204

AC:

708

AN:

3478

EpiCase

AF:

0.199

EpiControl

AF:

0.200

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 23, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 24, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.016

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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