8-85332503-G-T

Variant names:

• chr8-85332503-G-T
• NM_001128831.4:c.500C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001128831.4(CA1):​c.500C>A​(p.Ala167Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CA1 NM_001128831.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20186654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA1	NM_001128831.4	c.500C>A	p.Ala167Glu	missense_variant	Exon 6 of 8	ENST00000523022.6	NP_001122303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA1	ENST00000523022.6	c.500C>A	p.Ala167Glu	missense_variant	Exon 6 of 8	1	NM_001128831.4	ENSP00000429798.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460186 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726450

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.8
DANN	Benign	0.49
DEOGEN2	Benign	0.053	T;T;T;T;T;.;T;.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.57	.;.;.;T;T;T;T;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;L;L;.;.;.;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.092
Sift	Benign	0.31	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.85	T;T;T;T;.;T;.;.;.
Polyphen		0.0050	B;B;B;B;.;.;.;.;.
Vest4		0.15
MutPred		0.50		Gain of disorder (P = 0.0448);Gain of disorder (P = 0.0448);Gain of disorder (P = 0.0448);Gain of disorder (P = 0.0448);.;Gain of disorder (P = 0.0448);.;.;Gain of disorder (P = 0.0448);
MVP		0.71
MPC		0.032
ClinPred		0.10	T
GERP RS		1.4
Varity_R		0.37
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-86244732;