Variant chr17-60149988-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000717.5(CA4):c.-47C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,541,598 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

CA4
NM_000717.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.684

Variant links:

Genes affected

CA4 (HGNC:1375): (carbonic anhydrase 4) 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 gene encodes a glycosylphosphatidyl-inositol-anchored membrane isozyme expressed on the luminal surfaces of pulmonary (and certain other) capillaries and proximal renal tubules. Its exact function is not known; however, it may have a role in inherited renal abnormalities of bicarbonate transport. [provided by RefSeq, Jul 2008]

CA4 links:

CA4 (HGNC:):

CA4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 17-60149988-C-G is Benign according to our data. Variant chr17-60149988-C-G is described in ClinVar as [Benign]. Clinvar id is 324224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00263 (401/152318) while in subpopulation AFR AF= 0.00888 (369/41576). AF 95% confidence interval is 0.00813. There are 2 homozygotes in gnomad4. There are 193 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 401 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CA4	NM_000717.5 linkuse as main transcript	c.-47C>G		5_prime_UTR_variant	1/8	ENST00000300900.9	NP_000708.1	P22748-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA4	ENST00000300900.9 linkuse as main transcript	c.-47C>G		5_prime_UTR_variant	1/8	1	NM_000717.5	ENSP00000300900.3		P22748-1

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

400

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00888

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000733

AC:

151

AN:

206040

Hom.:

AF XY:

0.000566

AC XY:

AN XY:

114852

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000353

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000109

Gnomad OTH exome

AF:

0.000571

GnomAD4 exome

AF:

0.000284

AC:

395

AN:

1389280

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

167

AN XY:

693326

show subpopulations

Gnomad4 AFR exome

AF:

0.00848

Gnomad4 AMR exome

AF:

0.000973

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000254

Gnomad4 OTH exome

AF:

0.000846

GnomAD4 genome

AF:

0.00263

AC:

401

AN:

152318

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00888

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.00282

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.1

DANN

Benign

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over