Genetic Variant ENST00000654303.1:n.25_32dupGGGGCTCC (chr8-85463769-A-AGGAGCCCC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000654303.1(CA3-AS1):n.25_32dupGGGGCTCC 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 0.502 in 231,744 control chromosomes in the GnomAD database, including 33,341 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.57 ( 24746 hom., cov: 0)

Exomes 𝑓: 0.38 ( 8595 hom. )

Consequence

CA3-AS1
ENST00000654303.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00800

Publications

0 publications found

Variant links:

COSMIC-nc: COSV53405874

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 8-85463769-A-AGGAGCCCC is Benign according to our data. Variant chr8-85463769-A-AGGAGCCCC is described in ClinVar as Benign. ClinVar VariationId is 1225462.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

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+812dupGGGGCTCC	intron	N/A
CA3-AS1	NR_121631.1		n.106+451_106+458dupGGGGCTCC	intron	N/A
CA2	NM_000067.3	MANE Select	c.-313_-312insGGAGCCCC	upstream_gene	N/A	NP_000058.1	P00918

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CA3-AS1	ENST00000654303.1		n.25_32dupGGGGCTCC	non_coding_transcript_exon	Exon 1 of 3
CA3-AS1	ENST00000517697.7	TSL:4	n.193+451_193+458dupGGGGCTCC	intron	N/A
CA3-AS1	ENST00000521761.6	TSL:4	n.334+805_334+812dupGGGGCTCC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

84047

AN:

146442

Hom.:

24730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.633

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.524

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.693

Gnomad MID

AF:

0.638

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.587

GnomAD4 exome

AF:

0.380

AC:

32354

AN:

85216

Hom.:

8595

AF XY:

0.367

AC XY:

17148

AN XY:

46706

show subpopulations

African (AFR)

AF:

0.356

AC:

343

AN:

964

American (AMR)

AF:

0.200

AC:

198

AN:

990

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

690

AN:

2258

East Asian (EAS)

AF:

0.0666

AC:

289

AN:

4340

South Asian (SAS)

AF:

0.308

AC:

4648

AN:

15114

European-Finnish (FIN)

AF:

0.483

AC:

2267

AN:

4690

Middle Eastern (MID)

AF:

0.414

AC:

140

AN:

338

European-Non Finnish (NFE)

AF:

0.424

AC:

21933

AN:

51690

Other (OTH)

AF:

0.382

AC:

1846

AN:

4832

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

621

1242

1862

2483

3104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.574

AC:

84090

AN:

146528

Hom.:

24746

Cov.:

AF XY:

0.576

AC XY:

41147

AN XY:

71450

show subpopulations

African (AFR)

AF:

0.632

AC:

25092

AN:

39692

American (AMR)

AF:

0.524

AC:

7856

AN:

15000

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

1903

AN:

3414

East Asian (EAS)

AF:

0.387

AC:

1854

AN:

4792

South Asian (SAS)

AF:

0.390

AC:

1820

AN:

4670

European-Finnish (FIN)

AF:

0.693

AC:

6824

AN:

9842

Middle Eastern (MID)

AF:

0.638

AC:

171

AN:

268

European-Non Finnish (NFE)

AF:

0.560

AC:

36939

AN:

65936

Other (OTH)

AF:

0.587

AC:

1194

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1675

3349

5024

6698

8373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.380

Hom.:

792

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0080

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over