chr1-8949411-G-C

Variant names:

• chr1-8949411-G-C
• rs2274330
• NM_001215.4:c.228G>C

Variant summary

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

The NM_001215.4(CA6):​c.228G>C​(p.Gly76Gly) 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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 11 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001215.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA6	NM_001215.4	MANE Select	c.228G>C	p.Gly76Gly	synonymous	Exon 2 of 8	NP_001206.2	P23280-1
	CA6	NM_001270500.2		c.228G>C	p.Gly76Gly	synonymous	Exon 2 of 8	NP_001257429.1	P23280-2
	CA6	NM_001270501.2		c.79+3446G>C		intron	N/A	NP_001257430.1	P23280-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA6	ENST00000377443.7	TSL:1 MANE Select	c.228G>C	p.Gly76Gly	synonymous	Exon 2 of 8	ENSP00000366662.2	P23280-1
	CA6	ENST00000377436.6	TSL:1	c.228G>C	p.Gly76Gly	synonymous	Exon 2 of 8	ENSP00000366654.3	P23280-2
	CA6	ENST00000480186.7	TSL:2	c.228G>C	p.Gly76Gly	synonymous	Exon 2 of 3	ENSP00000435280.1	Q8N4G4

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

GnomAD2 exomes AF: 0.138 AC: 34419 AN: 249508 AF XY: 0.134

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 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

African (AFR) AF: 0.504 AC: 16795 AN: 33320

American (AMR) AF: 0.0734 AC: 3273 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3120 AN: 26060

East Asian (EAS) AF: 0.193 AC: 7627 AN: 39592

South Asian (SAS) AF: 0.171 AC: 14682 AN: 86008

European-Finnish (FIN) AF: 0.0812 AC: 4335 AN: 53388

Middle Eastern (MID) AF: 0.136 AC: 782 AN: 5752

European-Non Finnish (NFE) AF: 0.109 AC: 120578 AN: 1108964

Other (OTH) AF: 0.143 AC: 8601 AN: 60258

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

African (AFR) AF: 0.494 AC: 20440 AN: 41338

American (AMR) AF: 0.121 AC: 1845 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3468

East Asian (EAS) AF: 0.173 AC: 893 AN: 5172

South Asian (SAS) AF: 0.166 AC: 797 AN: 4812

European-Finnish (FIN) AF: 0.0811 AC: 860 AN: 10604

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7435 AN: 68020

Other (OTH) AF: 0.175 AC: 368 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.36
DANN	Benign	0.38
PhyloP100		-0.91
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: rs2274330; hg19: chr1-9009470; COSMIC: COSV66261627;