rs7821248

Variant names:

• chr8-85333547-G-A
• rs7821248
• NM_001128831.4:c.428C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-85333547-G-A
• chr8-85333547-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001128831.4(CA1):​c.428C>T​(p.Ala143Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,611,646 control chromosomes in the GnomAD database, including 340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (184 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (156 hom.)
• Consequence: CA1 NM_001128831.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.38
• Publications: 12 publications found

Genes affected

CA1 (HGNC:1368): (carbonic anhydrase 1) Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. This CA1 gene is closely linked to the CA2 and CA3 genes on chromosome 8. It encodes a cytosolic protein that is found at the highest level in erythrocytes. Allelic variants of this gene have been described in some populations. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Nov 2016]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006014228).
• BP6: Variant 8-85333547-G-A is Benign according to our data. Variant chr8-85333547-G-A is described in ClinVar as Benign. ClinVar VariationId is 776361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128831.4. 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
	CA1	NM_001128831.4	MANE Select	c.428C>T	p.Ala143Val	missense	Exon 5 of 8	NP_001122303.1	P00915
	CA1	NM_001128829.4		c.428C>T	p.Ala143Val	missense	Exon 6 of 9	NP_001122301.1	P00915
	CA1	NM_001128830.4		c.428C>T	p.Ala143Val	missense	Exon 6 of 9	NP_001122302.1	P00915

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA1	ENST00000523022.6	TSL:1 MANE Select	c.428C>T	p.Ala143Val	missense	Exon 5 of 8	ENSP00000429798.1	P00915
	CA1	ENST00000523953.5	TSL:1	c.428C>T	p.Ala143Val	missense	Exon 6 of 9	ENSP00000430656.1	P00915
	CA1	ENST00000517618.5	TSL:1	c.428C>T	p.Ala143Val	missense	Exon 4 of 7	ENSP00000430861.1	E5RHP7

Frequencies

GnomAD3 genomes AF: 0.0267 AC: 4066 AN: 152138 Hom.: 181 Cov.: 32

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0253

GnomAD2 exomes AF: 0.00683 AC: 1713 AN: 250640 AF XY: 0.00490

Gnomad AFR exome AF: 0.0919

Gnomad AMR exome AF: 0.00475

Gnomad ASJ exome AF: 0.000795

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000230

Gnomad OTH exome AF: 0.00262

GnomAD4 exome AF: 0.00283 AC: 4136 AN: 1459388 Hom.: 156 Cov.: 29 AF XY: 0.00250 AC XY: 1815 AN XY: 726126

African (AFR) AF: 0.0961 AC: 3206 AN: 33368

American (AMR) AF: 0.00550 AC: 246 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.000537 AC: 14 AN: 26090

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39574

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00782 AC: 45 AN: 5754

European-Non Finnish (NFE) AF: 0.000156 AC: 173 AN: 1110126

Other (OTH) AF: 0.00693 AC: 418 AN: 60282

GnomAD4 genome AF: 0.0268 AC: 4086 AN: 152258 Hom.: 184 Cov.: 32 AF XY: 0.0254 AC XY: 1891 AN XY: 74454

African (AFR) AF: 0.0928 AC: 3852 AN: 41526

American (AMR) AF: 0.0105 AC: 160 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68024

Other (OTH) AF: 0.0250 AC: 53 AN: 2116

Alfa AF: 0.0107 Hom.: 57

Bravo AF: 0.0300

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0865 AC: 381

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00850 AC: 1032

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.00

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
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.060
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.4
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.011	D
Polyphen		0.96	D
Vest4		0.32
MVP		0.83
MPC		0.040
ClinPred		0.071	T
GERP RS		2.2
Varity_R		0.56
gMVP		0.82
Mutation Taster		=84/16	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7821248; hg19: chr8-86245776;