1-8949393-C-T

Variant names:

• chr1-8949393-C-T
• rs61746465
• NM_001215.4:c.210C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001215.4(CA6):​c.210C>T​(p.Gly70Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,613,222 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (46 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (55 hom.)
• Consequence: CA6 NM_001215.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.217
• Publications: 1 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 1-8949393-C-T is Benign according to our data. Variant chr1-8949393-C-T is described in ClinVar as Benign. ClinVar VariationId is 784928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.217 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1625/152216) while in subpopulation AFR AF = 0.0375 (1556/41470). AF 95% confidence interval is 0.036. There are 46 homozygotes in GnomAd4. There are 777 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

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.210C>T	p.Gly70Gly	synonymous	Exon 2 of 8	NP_001206.2	P23280-1
	CA6	NM_001270500.2		c.210C>T	p.Gly70Gly	synonymous	Exon 2 of 8	NP_001257429.1	P23280-2
	CA6	NM_001270501.2		c.79+3428C>T		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.210C>T	p.Gly70Gly	synonymous	Exon 2 of 8	ENSP00000366662.2	P23280-1
	CA6	ENST00000377436.6	TSL:1	c.210C>T	p.Gly70Gly	synonymous	Exon 2 of 8	ENSP00000366654.3	P23280-2
	CA6	ENST00000480186.7	TSL:2	c.210C>T	p.Gly70Gly	synonymous	Exon 2 of 3	ENSP00000435280.1	Q8N4G4

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1617 AN: 152098 Hom.: 44 Cov.: 33

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00622

GnomAD2 exomes AF: 0.00274 AC: 687 AN: 250312 AF XY: 0.00213

Gnomad AFR exome AF: 0.0365

Gnomad AMR exome AF: 0.00187

Gnomad ASJ exome AF: 0.0000997

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00133 AC: 1942 AN: 1461006 Hom.: 55 Cov.: 33 AF XY: 0.00113 AC XY: 821 AN XY: 726838

African (AFR) AF: 0.0452 AC: 1509 AN: 33378

American (AMR) AF: 0.00204 AC: 91 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5764

European-Non Finnish (NFE) AF: 0.0000918 AC: 102 AN: 1111536

Other (OTH) AF: 0.00316 AC: 191 AN: 60368

GnomAD4 genome AF: 0.0107 AC: 1625 AN: 152216 Hom.: 46 Cov.: 33 AF XY: 0.0104 AC XY: 777 AN XY: 74458

African (AFR) AF: 0.0375 AC: 1556 AN: 41470

American (AMR) AF: 0.00314 AC: 48 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00548 Hom.: 12

Bravo AF: 0.0126

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.6
DANN	Benign	0.41
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs61746465; hg19: chr1-9009452;