1-8957145-A-G

Variant names:

• chr1-8957145-A-G
• rs2274333
• NM_001215.4:c.268A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001215.4(CA6):​c.268A>G​(p.Ser90Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,607,150 control chromosomes in the GnomAD database, including 80,525 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.27 (6383 hom., cov: 32)
  • Exomes 𝑓: 0.31 (74142 hom.)
• Consequence: CA6 NM_001215.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.3385882E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA6	NM_001215.4	c.268A>G	p.Ser90Gly	missense_variant	Exon 3 of 8	ENST00000377443.7	NP_001206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA6	ENST00000377443.7	c.268A>G	p.Ser90Gly	missense_variant	Exon 3 of 8	1	NM_001215.4	ENSP00000366662.2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41696 AN: 151900 Hom.: 6376 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.290

GnomAD3 exomes AF: 0.336 AC: 82849 AN: 246652 Hom.: 15217 AF XY: 0.338 AC XY: 45035 AN XY: 133272

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.433

Gnomad ASJ exome AF: 0.312

Gnomad EAS exome AF: 0.557

Gnomad SAS exome AF: 0.412

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.313 AC: 455196 AN: 1455132 Hom.: 74142 Cov.: 33 AF XY: 0.316 AC XY: 228563 AN XY: 723228

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.427

Gnomad4 ASJ exome AF: 0.305

Gnomad4 EAS exome AF: 0.534

Gnomad4 SAS exome AF: 0.409

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.274 AC: 41721 AN: 152018 Hom.: 6383 Cov.: 32 AF XY: 0.278 AC XY: 20634 AN XY: 74282

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.289

Alfa AF: 0.301 Hom.: 12653

Bravo AF: 0.279

TwinsUK AF: 0.287 AC: 1065

ALSPAC AF: 0.303 AC: 1168

ESP6500AA AF: 0.159 AC: 701

ESP6500EA AF: 0.296 AC: 2548

ExAC AF: 0.325 AC: 39447

Asia WGS AF: 0.449 AC: 1562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	.;T;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.58	T;D;D;D
MetaRNN	Benign	0.00023	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	.;M;M;.
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.17
Sift	Benign	0.11	T;T;T;T
Sift4G	Benign	0.085	T;T;T;T
Polyphen		0.97	.;D;.;.
Vest4		0.095, 0.086, 0.13
MPC		0.38
ClinPred		0.017	T
GERP RS		-0.41
Varity_R		0.21
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2274333; hg19: chr1-9017204;