chr8-85463769-A-AGGAGCCCC

Variant names:

• chr8-85463769-A-AGGAGCCCC
• rs77895131
• ENST00000654303.1:n.25_32dupGGGGCTCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00800

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA3-AS1	NR_121630.1	n.334+805_334+812dupGGGGCTCC		intron_variant	Intron 1 of 2
CA3-AS1	NR_121631.1	n.106+451_106+458dupGGGGCTCC		intron_variant	Intron 1 of 2
CA2	NM_000067.3	c.-313_-312insGGAGCCCC		upstream_gene_variant		ENST00000285379.10	NP_000058.1
CA2	NM_001293675.2	c.-497_-496insGGAGCCCC		upstream_gene_variant			NP_001280604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA2	ENST00000285379.10	c.-313_-312insGGAGCCCC		upstream_gene_variant		1	NM_000067.3	ENSP00000285379.4

Frequencies

GnomAD3 genomes AF: 0.574 AC: 84047 AN: 146442 Hom.: 24730 Cov.: 0

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

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.0666

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.574 AC: 84090 AN: 146528 Hom.: 24746 Cov.: 0 AF XY: 0.576 AC XY: 41147 AN XY: 71450

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.587

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 11, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77895131; hg19: chr8-86375998;