16-87897675-A-G

Variant names:

• chr16-87897675-A-G
• rs8058389
• NM_001739.2:c.618+4237T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001739.2(CA5A):​c.618+4237T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,160 control chromosomes in the GnomAD database, including 9,740 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9740 hom., cov: 33)
• Consequence: CA5A NM_001739.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001739.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA5A	NM_001739.2	MANE Select	c.618+4237T>C		intron	N/A	NP_001730.1
	CA5A	NM_001367225.1		c.618+4237T>C		intron	N/A	NP_001354154.1
	CA5A	NR_159798.1		n.698-3949T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA5A	ENST00000649794.3	MANE Select	c.618+4237T>C		intron	N/A	ENSP00000498065.2
	CA5A	ENST00000649158.1		c.618+4237T>C		intron	N/A	ENSP00000496993.1
	CA5A	ENST00000648177.1		c.436+4750T>C		intron	N/A	ENSP00000497626.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51150 AN: 152042 Hom.: 9705 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.337 AC: 51229 AN: 152160 Hom.: 9740 Cov.: 33 AF XY: 0.333 AC XY: 24751 AN XY: 74396

African (AFR) AF: 0.523 AC: 21716 AN: 41492

American (AMR) AF: 0.264 AC: 4036 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3466

East Asian (EAS) AF: 0.148 AC: 767 AN: 5186

South Asian (SAS) AF: 0.356 AC: 1711 AN: 4812

European-Finnish (FIN) AF: 0.201 AC: 2135 AN: 10610

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18770 AN: 67996

Other (OTH) AF: 0.317 AC: 669 AN: 2108

Alfa AF: 0.290 Hom.: 24135

Bravo AF: 0.348

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.26
DANN	Benign	0.38
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8058389; hg19: chr16-87931281;