8-85463769-AGGAGCCCCGGAGCCCCGGAGCCCC-AGGAGCCCCGGAGCCCC

Variant names:

• chr8-85463769-AGGAGCCCC-A
• rs77895131
• ENST00000654303.1:n.25_32delGGGGCTCC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28

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 -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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA3-AS1	NR_121630.1	n.334+805_334+812delGGGGCTCC		intron_variant	Intron 1 of 2
CA3-AS1	NR_121631.1	n.106+451_106+458delGGGGCTCC		intron_variant	Intron 1 of 2
CA2	NM_000067.3	c.-312_-305delGGAGCCCC		upstream_gene_variant		ENST00000285379.10	NP_000058.1
CA2	NM_001293675.2	c.-496_-489delGGAGCCCC		upstream_gene_variant			NP_001280604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA2	ENST00000285379.10	c.-312_-305delGGAGCCCC		upstream_gene_variant		1	NM_000067.3	ENSP00000285379.4

Frequencies

GnomAD3 genomes AF: 0.00176 AC: 258 AN: 146580 Hom.: 6 Cov.: 0

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.: 9 AF XY: 0.00630 AC XY: 296 AN XY: 47016

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0219

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000231

Gnomad4 OTH exome AF: 0.00206

GnomAD4 genome AF: 0.00177 AC: 259 AN: 146666 Hom.: 6 Cov.: 0 AF XY: 0.00221 AC XY: 158 AN XY: 71514

Gnomad4 AFR AF: 0.00289

Gnomad4 AMR AF: 0.00107

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0242

Gnomad4 FIN AF: 0.000203

Gnomad4 NFE AF: 0.000182

Gnomad4 OTH AF: 0.000491

ClinVar

Not reported in ClinVar

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;