1-8949392-G-C

Variant names:

• chr1-8949392-G-C
• rs2274329
• NM_001215.4:c.209G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001215.4(CA6):​c.209G>C​(p.Gly70Ala) variant causes a missense change. The variant allele was found at a frequency of 0.096 in 1,610,582 control chromosomes in the GnomAD database, including 8,499 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. Synonymous variant affecting the same amino acid position (i.e. G70G) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.073 (551 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7948 hom.)
• Consequence: CA6 NM_001215.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025099218).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 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.209G>C	p.Gly70Ala	missense	Exon 2 of 8	NP_001206.2	P23280-1
	CA6	NM_001270500.2		c.209G>C	p.Gly70Ala	missense	Exon 2 of 8	NP_001257429.1	P23280-2
	CA6	NM_001270501.2		c.79+3427G>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.209G>C	p.Gly70Ala	missense	Exon 2 of 8	ENSP00000366662.2	P23280-1
	CA6	ENST00000377436.6	TSL:1	c.209G>C	p.Gly70Ala	missense	Exon 2 of 8	ENSP00000366654.3	P23280-2
	CA6	ENST00000480186.7	TSL:2	c.209G>C	p.Gly70Ala	missense	Exon 2 of 3	ENSP00000435280.1	Q8N4G4

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11126 AN: 152078 Hom.: 555 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0837

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.0688

GnomAD2 exomes AF: 0.0931 AC: 23267 AN: 250018 AF XY: 0.0990

Gnomad AFR exome AF: 0.0166

Gnomad AMR exome AF: 0.0356

Gnomad ASJ exome AF: 0.0973

Gnomad EAS exome AF: 0.175

Gnomad FIN exome AF: 0.0775

Gnomad NFE exome AF: 0.0917

Gnomad OTH exome AF: 0.0922

GnomAD4 exome AF: 0.0984 AC: 143505 AN: 1458386 Hom.: 7948 Cov.: 33 AF XY: 0.101 AC XY: 73058 AN XY: 725648

African (AFR) AF: 0.0143 AC: 479 AN: 33388

American (AMR) AF: 0.0371 AC: 1653 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 2635 AN: 26072

East Asian (EAS) AF: 0.192 AC: 7626 AN: 39636

South Asian (SAS) AF: 0.163 AC: 14059 AN: 86018

European-Finnish (FIN) AF: 0.0768 AC: 4102 AN: 53404

Middle Eastern (MID) AF: 0.101 AC: 581 AN: 5750

European-Non Finnish (NFE) AF: 0.0959 AC: 106345 AN: 1109242

Other (OTH) AF: 0.100 AC: 6025 AN: 60274

GnomAD4 genome AF: 0.0731 AC: 11120 AN: 152196 Hom.: 551 Cov.: 32 AF XY: 0.0738 AC XY: 5494 AN XY: 74434

African (AFR) AF: 0.0168 AC: 697 AN: 41494

American (AMR) AF: 0.0529 AC: 808 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3472

East Asian (EAS) AF: 0.172 AC: 888 AN: 5170

South Asian (SAS) AF: 0.160 AC: 770 AN: 4824

European-Finnish (FIN) AF: 0.0759 AC: 806 AN: 10626

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0961 AC: 6538 AN: 68006

Other (OTH) AF: 0.0700 AC: 148 AN: 2114

Alfa AF: 0.0903 Hom.: 552

Bravo AF: 0.0680

TwinsUK AF: 0.0992 AC: 368

ALSPAC AF: 0.106 AC: 407

ESP6500AA AF: 0.0209 AC: 92

ESP6500EA AF: 0.0953 AC: 820

ExAC AF: 0.0924 AC: 11212

Asia WGS AF: 0.146 AC: 505 AN: 3478

EpiCase AF: 0.0999

EpiControl AF: 0.0916

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.7
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.23
MPC		0.67
ClinPred		0.051	T
GERP RS		3.4
Varity_R		0.28
gMVP		0.70
Mutation Taster		=96/4	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: rs2274329; hg19: chr1-9009451; COSMIC: COSV66261780;