rs2274330

Positions:

• chr1-8949411-G-C
• chr1-8949411-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001215.4(CA6):​c.228G>C​(p.Gly76=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,609,944 control chromosomes in the GnomAD database, including 20,427 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (5920 hom., cov: 32)
  • Exomes 𝑓: 0.12 (14507 hom.)
• Consequence: CA6 NM_001215.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905

Genes affected

CA6 (HGNC:1380): (carbonic anhydrase 6) The protein encoded by this gene is one of several isozymes of carbonic anhydrase. This protein is found only in salivary glands and saliva and protein may play a role in the reversible hydratation of carbon dioxide though its function in saliva is unknown. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.905 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA6	NM_001215.4	c.228G>C	p.Gly76=	synonymous_variant	2/8	ENST00000377443.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA6	ENST00000377443.7	c.228G>C	p.Gly76=	synonymous_variant	2/8	1	NM_001215.4	P2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33097 AN: 151900 Hom.: 5893 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.174

GnomAD3 exomes AF: 0.138 AC: 34419 AN: 249508 Hom.: 3778 AF XY: 0.134 AC XY: 18147 AN XY: 135042

Gnomad AFR exome AF: 0.507

Gnomad AMR exome AF: 0.0667

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.175

Gnomad SAS exome AF: 0.172

Gnomad FIN exome AF: 0.0824

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.123 AC: 179793 AN: 1457926 Hom.: 14507 Cov.: 33 AF XY: 0.124 AC XY: 89697 AN XY: 725446

Gnomad4 AFR exome AF: 0.504

Gnomad4 AMR exome AF: 0.0734

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.0812

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.218 AC: 33171 AN: 152018 Hom.: 5920 Cov.: 32 AF XY: 0.214 AC XY: 15942 AN XY: 74336

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0811

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.175

Alfa AF: 0.140 Hom.: 709

Bravo AF: 0.232

Asia WGS AF: 0.186 AC: 647 AN: 3478

EpiCase AF: 0.114

EpiControl AF: 0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.36
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2274330; hg19: chr1-9009470; COSMIC: COSV66261627;