1-8970905-C-T

Variant names:

• chr1-8970905-C-T
• rs3737665
• NM_001215.4:c.768C>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.768C>T​(p.Asn256Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,612,046 control chromosomes in the GnomAD database, including 43,659 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 0.21 (3920 hom., cov: 31)
  • Exomes 𝑓: 0.22 (39739 hom.)
• Consequence: CA6 NM_001215.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917

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]

ENSG00000290109 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.917 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA6	NM_001215.4	c.768C>T	p.Asn256Asn	synonymous_variant	Exon 7 of 8	ENST00000377443.7	NP_001206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA6	ENST00000377443.7	c.768C>T	p.Asn256Asn	synonymous_variant	Exon 7 of 8	1	NM_001215.4	ENSP00000366662.2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32658 AN: 151958 Hom.: 3913 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.237

GnomAD3 exomes AF: 0.256 AC: 64428 AN: 251462 Hom.: 9713 AF XY: 0.256 AC XY: 34834 AN XY: 135902

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.322

Gnomad ASJ exome AF: 0.264

Gnomad EAS exome AF: 0.545

Gnomad SAS exome AF: 0.320

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.223 AC: 325898 AN: 1459970 Hom.: 39739 Cov.: 32 AF XY: 0.226 AC XY: 164381 AN XY: 726382

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.320

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.507

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.215 AC: 32683 AN: 152076 Hom.: 3920 Cov.: 31 AF XY: 0.220 AC XY: 16317 AN XY: 74326

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.237

Alfa AF: 0.218 Hom.: 7665

Bravo AF: 0.223

Asia WGS AF: 0.402 AC: 1399 AN: 3478

EpiCase AF: 0.214

EpiControl AF: 0.217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.82
DANN	Benign	0.50

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: rs3737665; hg19: chr1-9030964; COSMIC: COSV66263035; COSMIC: COSV66263035;