Genetic Variant CA3-AS1:n.25_32delGGGGCTCC (chr8-85463769-AGGAGCCCC-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The ENST00000654303.1(CA3-AS1):n.25_32delGGGGCTCC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 232,476 control chromosomes in the GnomAD database, including 15 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0018 ( 6 hom., cov: 0)

Exomes 𝑓: 0.0042 ( 9 hom. )

Consequence

CA3-AS1
ENST00000654303.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.28

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive osteopetrosis 3
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

CA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00177 (259/146666) while in subpopulation SAS AF = 0.0242 (113/4676). AF 95% confidence interval is 0.0206. There are 6 homozygotes in GnomAd4. There are 158 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000654303.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CA3-AS1	NR_121630.1		n.334+805_334+812delGGGGCTCC	intron	N/A
CA3-AS1	NR_121631.1		n.106+451_106+458delGGGGCTCC	intron	N/A
CA2	NM_000067.3	MANE Select	c.-312_-305delGGAGCCCC	upstream_gene	N/A	NP_000058.1	P00918

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CA3-AS1	ENST00000654303.1		n.25_32delGGGGCTCC	non_coding_transcript_exon	Exon 1 of 3
CA3-AS1	ENST00000517697.7	TSL:4	n.193+451_193+458delGGGGCTCC	intron	N/A
CA3-AS1	ENST00000521761.6	TSL:4	n.334+805_334+812delGGGGCTCC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

258

AN:

146580

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00288

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00107

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0241

Gnomad FIN

AF:

0.000203

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000182

Gnomad OTH

AF:

0.000497

GnomAD4 exome

AF:

0.00418

AC:

359

AN:

85810

Hom.:

AF XY:

0.00630

AC XY:

296

AN XY:

47016

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

966

American (AMR)

AF:

0.00101

AC:

AN:

992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2268

East Asian (EAS)

AF:

0.00

AC:

AN:

4344

South Asian (SAS)

AF:

0.0219

AC:

334

AN:

15286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4722

Middle Eastern (MID)

AF:

0.00592

AC:

AN:

338

European-Non Finnish (NFE)

AF:

0.000231

AC:

AN:

52038

Other (OTH)

AF:

0.00206

AC:

AN:

4856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.572

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00177

AC:

259

AN:

146666

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

158

AN XY:

71514

show subpopulations

African (AFR)

AF:

0.00289

AC:

115

AN:

39752

American (AMR)

AF:

0.00107

AC:

AN:

15004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3416

East Asian (EAS)

AF:

0.00

AC:

AN:

4798

South Asian (SAS)

AF:

0.0242

AC:

113

AN:

4676

European-Finnish (FIN)

AF:

0.000203

AC:

AN:

9852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.000182

AC:

AN:

65984

Other (OTH)

AF:

0.000491

AC:

AN:

2036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000155

Hom.:

792

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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8-85463769-AGGAGCCCCGGAGCCCCGGAGCCCC-AGGAGCCCCGGAGCCCC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over