dbSNP rs543743714: CA4:c.-76G>A (chr17-60149959-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000591725.1(CA4):c.-434G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000004 in 1,251,268 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

CA4
ENST00000591725.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.756

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

retinitis pigmentosa 17
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P

CA4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000591725.1. 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
	CA4	NM_000717.5	MANE Select	c.-76G>A		upstream_gene	N/A	NP_000708.1	P22748-1
	CA4	NR_137422.2		n.-14G>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CA4	ENST00000904866.1		c.-76G>A	5_prime_UTR	Exon 1 of 9	ENSP00000574925.1
CA4	ENST00000591725.1	TSL:3	c.-434G>A	5_prime_UTR	Exon 1 of 5	ENSP00000466964.1	K7ENI8
CA4	ENST00000957246.1		c.1-76G>A	intron	N/A	ENSP00000627305.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1099020

Hom.:

Cov.:

AF XY:

0.00000179

AC XY:

AN XY:

557474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26424

American (AMR)

AF:

0.00

AC:

AN:

38332

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23308

East Asian (EAS)

AF:

0.00

AC:

AN:

36206

South Asian (SAS)

AF:

0.00

AC:

AN:

75788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4990

European-Non Finnish (NFE)

AF:

0.00000495

AC:

AN:

808026

Other (OTH)

AF:

0.00

AC:

AN:

48344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.7

(source)

DANN

Benign

0.85

PhyloP100

-0.76

PromoterAI

-0.031

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over