dbSNP rs2274330: CA6:p.Gly76Gly (chr1-8949411-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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. 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.905

Publications

11 publications found

Variant links:

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]

CA6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA6	NM_001215.4 link	c.228G>C	p.Gly76Gly	synonymous_variant	Exon 2 of 8	ENST00000377443.7	NP_001206.2	P23280-1B4DUH8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA6	ENST00000377443.7 link	c.228G>C	p.Gly76Gly	synonymous_variant	Exon 2 of 8	1	NM_001215.4	ENSP00000366662.2		P23280-1
CA6	ENST00000480186.7 link	c.228G>C	p.Gly76Gly	synonymous_variant	Exon 2 of 3	2		ENSP00000435280.1		Q8N4G4

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33097

AN:

151900

Hom.:

5893

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.124

AC XY:

89697

AN XY:

725446

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

7362

14724

22087

29449

36811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4706

9412

14118

18824

23530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.218

AC:

33171

AN:

152018

Hom.:

5920

Cov.:

AF XY:

0.214

AC XY:

15942

AN XY:

74336

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7435

AN:

68020

Other (OTH)

AF:

0.175

AC:

368

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1090

2180

3269

4359

5449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.38

PhyloP100

-0.91

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over