8-85463769-A-AGGAGCCCCGGAGCCCC

Variant names:

• chr8-85463769-A-AGGAGCCCCGGAGCCCC
• rs77895131
• ENST00000654303.1:n.17_32dupGGGGCTCCGGGGCTCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000654303.1(CA3-AS1):​n.17_32dupGGGGCTCCGGGGCTCC 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 0.0256 in 232,340 control chromosomes in the GnomAD database, including 132 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (99 hom., cov: 0)
  • Exomes 𝑓: 0.020 (33 hom.)
• Consequence: CA3-AS1 ENST00000654303.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00800
• Publications: 0 publications found

Genes affected

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

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

ACMG classification

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

• BP6: Variant 8-85463769-A-AGGAGCCCCGGAGCCCC is Benign according to our data. Variant chr8-85463769-A-AGGAGCCCCGGAGCCCC is described in ClinVar as Likely_benign. ClinVar VariationId is 1190097.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0289 (4234/146648) while in subpopulation NFE AF = 0.0456 (3011/65968). AF 95% confidence interval is 0.0443. There are 99 homozygotes in GnomAd4. There are 1924 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 99 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA3-AS1	NR_121630.1		n.334+797_334+812dupGGGGCTCCGGGGCTCC		intron	N/A
	CA3-AS1	NR_121631.1		n.106+443_106+458dupGGGGCTCCGGGGCTCC		intron	N/A
	CA2	NM_000067.3	MANE Select	c.-313_-312insGGAGCCCCGGAGCCCC		upstream_gene	N/A	NP_000058.1	P00918

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA3-AS1	ENST00000654303.1		n.17_32dupGGGGCTCCGGGGCTCC		non_coding_transcript_exon	Exon 1 of 3
	CA3-AS1	ENST00000517697.7	TSL:4	n.193+443_193+458dupGGGGCTCCGGGGCTCC		intron	N/A
	CA3-AS1	ENST00000521761.6	TSL:4	n.334+797_334+812dupGGGGCTCCGGGGCTCC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4238 AN: 146562 Hom.: 100 Cov.: 0

Gnomad AFR AF: 0.00916

Gnomad AMI AF: 0.00455

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.000415

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.0207

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.0333

GnomAD4 exome AF: 0.0201 AC: 1722 AN: 85692 Hom.: 33 AF XY: 0.0191 AC XY: 895 AN XY: 46936

African (AFR) AF: 0.00414 AC: 4 AN: 966

American (AMR) AF: 0.00806 AC: 8 AN: 992

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 26 AN: 2268

East Asian (EAS) AF: 0.00 AC: 0 AN: 4344

South Asian (SAS) AF: 0.00812 AC: 124 AN: 15264

European-Finnish (FIN) AF: 0.0153 AC: 72 AN: 4716

Middle Eastern (MID) AF: 0.00592 AC: 2 AN: 338

European-Non Finnish (NFE) AF: 0.0267 AC: 1385 AN: 51956

Other (OTH) AF: 0.0208 AC: 101 AN: 4848

GnomAD4 genome AF: 0.0289 AC: 4234 AN: 146648 Hom.: 99 Cov.: 0 AF XY: 0.0269 AC XY: 1924 AN XY: 71506

African (AFR) AF: 0.00913 AC: 363 AN: 39754

American (AMR) AF: 0.0296 AC: 444 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 73 AN: 3416

East Asian (EAS) AF: 0.000417 AC: 2 AN: 4798

South Asian (SAS) AF: 0.0128 AC: 60 AN: 4676

European-Finnish (FIN) AF: 0.0208 AC: 205 AN: 9850

Middle Eastern (MID) AF: 0.0187 AC: 5 AN: 268

European-Non Finnish (NFE) AF: 0.0456 AC: 3011 AN: 65968

Other (OTH) AF: 0.0329 AC: 67 AN: 2034

Alfa AF: 0.0285 Hom.: 792

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0080
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs77895131; hg19: chr8-86375998;