dbSNP rs113734032: GUCA1B:c.*480G>A (chr6-42184335-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002098.6(GUCA1B):c.*480G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 220,812 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 165 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 8 hom. )

Consequence

GUCA1B
NM_002098.6 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.00400

Publications

2 publications found

Variant links:

Genes affected

GUCA1B (HGNC:4679): (guanylate cyclase activator 1B) The protein encoded by this gene is a calcium-binding protein that activates photoreceptor guanylate cyclases. This gene may have arisen due to a gene duplication event since there is a highly similar gene clustered with it on chromosome 6. Mutations in this gene can cause a form of retinitis pigmentosa. [provided by RefSeq, Nov 2009]

GUCA1B Gene-Disease associations (from GenCC):

retinitis pigmentosa 48
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GUCA1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-42184335-C-T is Benign according to our data. Variant chr6-42184335-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 356720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002098.6. 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
	GUCA1B	NM_002098.6	MANE Select	c.*480G>A		3_prime_UTR	Exon 4 of 4	NP_002089.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCA1B	ENST00000230361.4	TSL:1 MANE Select	c.*480G>A		3_prime_UTR	Exon 4 of 4	ENSP00000230361.3	Q9UMX6

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3884

AN:

152148

Hom.:

166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0870

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0273

GnomAD4 exome

AF:

0.00516

AC:

354

AN:

68546

Hom.:

AF XY:

0.00495

AC XY:

176

AN XY:

35584

show subpopulations

African (AFR)

AF:

0.0871

AC:

252

AN:

2892

American (AMR)

AF:

0.00961

AC:

AN:

4474

Ashkenazi Jewish (ASJ)

AF:

0.00132

AC:

AN:

1516

East Asian (EAS)

AF:

0.00

AC:

AN:

4150

South Asian (SAS)

AF:

0.000655

AC:

AN:

9154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2734

Middle Eastern (MID)

AF:

0.0123

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.000728

AC:

AN:

39814

Other (OTH)

AF:

0.00533

AC:

AN:

3568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0256

AC:

3895

AN:

152266

Hom.:

165

Cov.:

AF XY:

0.0245

AC XY:

1827

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0870

AC:

3616

AN:

41544

American (AMR)

AF:

0.0116

AC:

178

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68028

Other (OTH)

AF:

0.0270

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

184

368

553

737

921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0234

Hom.:

Bravo

AF:

0.0293

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cone dystrophy (1)

not provided (1)

Retinitis pigmentosa (1)

Retinitis Pigmentosa, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.5

(source)

DANN

Benign

0.83

PhyloP100

0.0040

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over