Genetic Variant CA3-AS1:n.193+327T>A (chr8-85463901-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000517697.6(CA3-AS1):n.193+327T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.984 in 550,414 control chromosomes in the GnomAD database, including 266,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 72383 hom., cov: 22)

Exomes 𝑓: 0.98 ( 194264 hom. )

Consequence

CA3-AS1
ENST00000517697.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.147

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 8-85463901-A-T is Benign according to our data. Variant chr8-85463901-A-T is described in ClinVar as [Benign]. Clinvar id is 369615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CA3-AS1	NR_121630.1 link	n.334+681T>A	intron_variant	Intron 1 of 2
CA3-AS1	NR_121631.1 link	n.106+327T>A	intron_variant	Intron 1 of 2
CA2	NM_000067.3 link	c.-181A>T	upstream_gene_variant		ENST00000285379.10	NP_000058.1	P00918V9HW21
CA2	NM_001293675.2 link	c.-365A>T	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.-181A>T		upstream_gene_variant		1	NM_000067.3	ENSP00000285379.4		P00918

Frequencies

GnomAD3 genomes

AF:

0.986

AC:

146745

AN:

148860

Hom.:

72331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.996

Gnomad AMI

AF:

0.952

Gnomad AMR

AF:

0.985

Gnomad ASJ

AF:

0.994

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.994

Gnomad FIN

AF:

0.994

Gnomad MID

AF:

0.990

Gnomad NFE

AF:

0.977

Gnomad OTH

AF:

0.991

GnomAD4 exome

AF:

0.984

AC:

394950

AN:

401450

Hom.:

194264

Cov.:

AF XY:

0.984

AC XY:

218597

AN XY:

222086

show subpopulations

Gnomad4 AFR exome

AF:

0.994

Gnomad4 AMR exome

AF:

0.991

Gnomad4 ASJ exome

AF:

0.990

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.993

Gnomad4 FIN exome

AF:

0.993

Gnomad4 NFE exome

AF:

0.978

Gnomad4 OTH exome

AF:

0.985

GnomAD4 genome

AF:

0.986

AC:

146849

AN:

148964

Hom.:

72383

Cov.:

AF XY:

0.986

AC XY:

71743

AN XY:

72766

show subpopulations

Gnomad4 AFR

AF:

0.996

Gnomad4 AMR

AF:

0.985

Gnomad4 ASJ

AF:

0.994

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.994

Gnomad4 FIN

AF:

0.994

Gnomad4 NFE

AF:

0.977

Gnomad4 OTH

AF:

0.991

Alfa

AF:

0.985

Hom.:

3223

Bravo

AF:

0.986

Asia WGS

AF:

0.997

AC:

3399

AN:

3410

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Osteopetrosis with renal tubular acidosis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.76

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