Variant 17-60150110-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000717.5(CA4):c.58+18G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000698 in 1,589,296 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00043 ( 3 hom. )

Consequence

CA4
NM_000717.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.04

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-60150110-G-C is Benign according to our data. Variant chr17-60150110-G-C is described in ClinVar as [Benign]. Clinvar id is 1170906.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-60150110-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00318 (485/152324) while in subpopulation AFR AF= 0.00977 (406/41570). AF 95% confidence interval is 0.00898. There are 2 homozygotes in gnomad4. There are 233 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 485 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA4	NM_000717.5 linkuse as main transcript	c.58+18G>C		intron_variant		ENST00000300900.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
CA4	ENST00000300900.9 linkuse as main transcript	c.58+18G>C	intron_variant	1	NM_000717.5	P1	P22748-1
CA4	ENST00000591725.1 linkuse as main transcript	c.-301+18G>C	intron_variant	3
CA4	ENST00000586876.1 linkuse as main transcript	c.58+18G>C	intron_variant, NMD_transcript_variant	2			P22748-2
CA4	ENST00000585705.5 linkuse as main transcript	n.151+18G>C	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00319

AC:

486

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00980

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.000705

AC:

149

AN:

211452

Hom.:

AF XY:

0.000525

AC XY:

AN XY:

118174

show subpopulations

Gnomad AFR exome

AF:

0.00752

Gnomad AMR exome

AF:

0.000990

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000341

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.000743

GnomAD4 exome

AF:

0.000435

AC:

625

AN:

1436972

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

272

AN XY:

715166

show subpopulations

Gnomad4 AFR exome

AF:

0.00813

Gnomad4 AMR exome

AF:

0.00118

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.0000259

Gnomad4 NFE exome

AF:

0.000227

Gnomad4 OTH exome

AF:

0.000771

GnomAD4 genome

AF:

0.00318

AC:

485

AN:

152324

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00977

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.00348

Asia WGS

AF:

0.000868

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.8

DANN

Benign

0.64

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