X-15764682-C-G

Variant names:

• chrX-15764682-C-G
• rs1379030882
• NM_007220.4:c.247C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_007220.4(CA5B):​c.247C>G​(p.Leu83Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,196,499 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L83R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000092 (0 hom., 1 hem., cov: 21)
  • Exomes 𝑓: 0.000012 (0 hom. 2 hem.)
• Consequence: CA5B NM_007220.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34
• Publications: 0 publications found

Genes affected

CA5B (HGNC:1378): (carbonic anhydrase 5B) 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. This gene encodes carbonic anhydrase 5B. CA5B, and the related CA5A gene, has its expression localized in the mitochondria though CA5B has a wider tissue distribution than CA5A, which is restricted to the liver, kidneys, and skeletal muscle. A carbonic anhydrase pseudogene (CA5BP1) is adjacent to the CA5B gene and these two loci produce CA5BP1-CA5B readthrough transcripts. [provided by RefSeq, Jan 2019]

CA5BP1-CA5B (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007220.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA5B	NM_007220.4	MANE Select	c.247C>G	p.Leu83Val	missense	Exon 3 of 8	NP_009151.1	Q9Y2D0
	CA5BP1-CA5B	NR_160544.1		n.1011C>G		non_coding_transcript_exon	Exon 6 of 12
	CA5BP1-CA5B	NR_160545.1		n.1011C>G		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA5B	ENST00000318636.8	TSL:1 MANE Select	c.247C>G	p.Leu83Val	missense	Exon 3 of 8	ENSP00000314099.3	Q9Y2D0
	CA5B	ENST00000948118.1		c.247C>G	p.Leu83Val	missense	Exon 3 of 9	ENSP00000618177.1
	CA5B	ENST00000479740.5	TSL:3	c.247C>G	p.Leu83Val	missense	Exon 2 of 3	ENSP00000417553.1	C9JA11

Frequencies

GnomAD3 genomes AF: 0.00000916 AC: 1 AN: 109221 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000190

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000120 AC: 13 AN: 1087278 Hom.: 0 Cov.: 28 AF XY: 0.00000565 AC XY: 2 AN XY: 353764

African (AFR) AF: 0.00 AC: 0 AN: 26231

American (AMR) AF: 0.00 AC: 0 AN: 34865

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19052

East Asian (EAS) AF: 0.00 AC: 0 AN: 30074

South Asian (SAS) AF: 0.00 AC: 0 AN: 53299

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40281

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4065

European-Non Finnish (NFE) AF: 0.0000156 AC: 13 AN: 833764

Other (OTH) AF: 0.00 AC: 0 AN: 45647

GnomAD4 genome AF: 0.00000916 AC: 1 AN: 109221 Hom.: 0 Cov.: 21 AF XY: 0.0000318 AC XY: 1 AN XY: 31473

African (AFR) AF: 0.00 AC: 0 AN: 29886

American (AMR) AF: 0.00 AC: 0 AN: 10126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2602

East Asian (EAS) AF: 0.00 AC: 0 AN: 3508

South Asian (SAS) AF: 0.00 AC: 0 AN: 2462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.0000190 AC: 1 AN: 52559

Other (OTH) AF: 0.00 AC: 0 AN: 1441

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.51
Sift	Benign	0.033	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.97	D
Vest4		0.43
MutPred		0.74		Gain of methylation at K81 (P = 0.0628)
MVP		0.84
MPC		2.5
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.39
gMVP		0.72
Mutation Taster		=85/15	polymorphism

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: rs1379030882; hg19: chrX-15782805;