chr1-8970905-C-T

Variant names:

• chr1-8970905-C-T
• rs3737665
• NM_001215.4:c.768C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000377443.7(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 ENST00000377443.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377443.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA6	NM_001215.4	MANE Select	c.768C>T	p.Asn256Asn	synonymous	Exon 7 of 8	NP_001206.2
	CA6	NM_001270500.2		c.768C>T	p.Asn256Asn	synonymous	Exon 7 of 8	NP_001257429.1
	CA6	NM_001270501.2		c.588C>T	p.Asn196Asn	synonymous	Exon 6 of 7	NP_001257430.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA6	ENST00000377443.7	TSL:1 MANE Select	c.768C>T	p.Asn256Asn	synonymous	Exon 7 of 8	ENSP00000366662.2
	CA6	ENST00000377436.6	TSL:1	c.768C>T	p.Asn256Asn	synonymous	Exon 7 of 8	ENSP00000366654.3
	CA6	ENST00000377442.3	TSL:1	c.588C>T	p.Asn196Asn	synonymous	Exon 6 of 7	ENSP00000366661.2

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

GnomAD2 exomes AF: 0.256 AC: 64428 AN: 251462 AF XY: 0.256

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 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

African (AFR) AF: 0.151 AC: 5049 AN: 33444

American (AMR) AF: 0.320 AC: 14327 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 6761 AN: 26120

East Asian (EAS) AF: 0.507 AC: 20113 AN: 39678

South Asian (SAS) AF: 0.318 AC: 27408 AN: 86218

European-Finnish (FIN) AF: 0.158 AC: 8439 AN: 53410

Middle Eastern (MID) AF: 0.334 AC: 1925 AN: 5766

European-Non Finnish (NFE) AF: 0.205 AC: 227622 AN: 1110304

Other (OTH) AF: 0.236 AC: 14254 AN: 60312

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

African (AFR) AF: 0.158 AC: 6560 AN: 41484

American (AMR) AF: 0.274 AC: 4174 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 900 AN: 3468

East Asian (EAS) AF: 0.539 AC: 2780 AN: 5162

South Asian (SAS) AF: 0.330 AC: 1594 AN: 4828

European-Finnish (FIN) AF: 0.161 AC: 1711 AN: 10596

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14198 AN: 67972

Other (OTH) AF: 0.237 AC: 499 AN: 2104

Alfa AF: 0.217 Hom.: 14752

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.82
DANN	Benign	0.50
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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