17-51976841-G-A

Variant names:

• chr17-51976841-G-A
• rs425459
• NM_020178.5:c.137-45709C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020178.5(CA10):​c.137-45709C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,040 control chromosomes in the GnomAD database, including 61,258 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 0.90 (61258 hom., cov: 32)
• Consequence: CA10 NM_020178.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 3 publications found

Genes affected

CA10 (HGNC:1369): (carbonic anhydrase 10) This gene encodes a protein that belongs to the carbonic anhydrase family of zinc metalloenzymes, which catalyze the reversible hydration of carbon dioxide in various biological processes. The protein encoded by this gene is an acatalytic member of the alpha-carbonic anhydrase subgroup, and it is thought to play a role in the central nervous system, especially in brain development. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA10	NM_020178.5	c.137-45709C>T		intron_variant	Intron 2 of 8	ENST00000451037.7	NP_064563.1
CA10	NM_001082533.1	c.137-45709C>T		intron_variant	Intron 3 of 9		NP_001076002.1
CA10	NM_001082534.2	c.137-45709C>T		intron_variant	Intron 3 of 9		NP_001076003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA10	ENST00000451037.7	c.137-45709C>T		intron_variant	Intron 2 of 8	1	NM_020178.5	ENSP00000405388.2

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136321 AN: 151922 Hom.: 61221 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.890

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.897 AC: 136414 AN: 152040 Hom.: 61258 Cov.: 32 AF XY: 0.896 AC XY: 66611 AN XY: 74318

African (AFR) AF: 0.846 AC: 35151 AN: 41526

American (AMR) AF: 0.925 AC: 14139 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3119 AN: 3470

East Asian (EAS) AF: 0.947 AC: 4904 AN: 5180

South Asian (SAS) AF: 0.832 AC: 4020 AN: 4830

European-Finnish (FIN) AF: 0.912 AC: 9603 AN: 10534

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.920 AC: 62486 AN: 67900

Other (OTH) AF: 0.888 AC: 1877 AN: 2114

Alfa AF: 0.911 Hom.: 32270

Bravo AF: 0.896

Asia WGS AF: 0.875 AC: 3028 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.32
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs425459; hg19: chr17-50054201;