Genetic Variant CA3-AS1:n.193+276G>T (chr8-85463952-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000517697.6(CA3-AS1):n.193+276G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 973,664 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0041 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 17 hom. )

Consequence

CA3-AS1
ENST00000517697.6 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0610

Variant links:

Genes affected

CA3-AS1 (HGNC:51657): (CA3 antisense RNA 1)

CA3-AS1 links:

CA2 (HGNC:1373): (carbonic anhydrase 2) The protein encoded by this gene is one of several isozymes of carbonic anhydrase, which catalyzes reversible hydration of carbon dioxide. Defects in this enzyme are associated with osteopetrosis and renal tubular acidosis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

CA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BS2

High Homozygotes in GnomAdExome4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CA3-AS1	NR_121630.1 link	n.334+630G>T	intron_variant	Intron 1 of 2
CA3-AS1	NR_121631.1 link	n.106+276G>T	intron_variant	Intron 1 of 2
CA2	NM_000067.3 link	c.-130C>A	upstream_gene_variant		ENST00000285379.10	NP_000058.1	P00918V9HW21
CA2	NM_001293675.2 link	c.-314C>A	upstream_gene_variant			NP_001280604.1	V9HW21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA2	ENST00000285379.10 link	c.-130C>A		upstream_gene_variant		1	NM_000067.3	ENSP00000285379.4		P00918

Frequencies

GnomAD3 genomes

AF:

0.00408

AC:

619

AN:

151800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00851

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00142

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00573

Gnomad OTH

AF:

0.00528

GnomAD4 exome

AF:

0.00512

AC:

4205

AN:

821758

Hom.:

Cov.:

AF XY:

0.00487

AC XY:

2074

AN XY:

426136

show subpopulations

Gnomad4 AFR exome

AF:

0.000871

AC:

AN:

19518

Gnomad4 AMR exome

AF:

0.00618

AC:

212

AN:

34330

Gnomad4 ASJ exome

AF:

0.000658

AC:

AN:

21276

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

32332

Gnomad4 SAS exome

AF:

0.00120

AC:

AN:

67318

Gnomad4 FIN exome

AF:

0.00160

AC:

AN:

33828

Gnomad4 NFE exome

AF:

0.00638

AC:

3641

AN:

570272

Gnomad4 Remaining exome

AF:

0.00469

AC:

184

AN:

39258

Heterozygous variant carriers

209

418

627

836

1045

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00407

AC:

619

AN:

151906

Hom.:

Cov.:

AF XY:

0.00405

AC XY:

301

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.00154

AC:

0.00154343

AN:

0.00154343

Gnomad4 AMR

AF:

0.00850

AC:

0.00849784

AN:

0.00849784

Gnomad4 ASJ

AF:

0.000866

AC:

0.000865551

AN:

0.000865551

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00145

AC:

0.00145349

AN:

0.00145349

Gnomad4 FIN

AF:

0.00142

AC:

0.00141831

AN:

0.00141831

Gnomad4 NFE

AF:

0.00573

AC:

0.0057307

AN:

0.0057307

Gnomad4 OTH

AF:

0.00522

AC:

0.00522317

AN:

0.00522317

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00538

Asia WGS

AF:

0.00116

AC:

AN:

3464

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Osteopetrosis with renal tubular acidosis

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.89

Mutation Taster

=289/11

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

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