chr6-42184312-C-T

Variant names:

• chr6-42184312-C-T
• rs13211352
• NM_002098.6:c.*503G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002098.6(GUCA1B):​c.*503G>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 0.0593 in 204,506 control chromosomes in the GnomAD database, including 469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (344 hom., cov: 32)
  • Exomes 𝑓: 0.064 (125 hom.)
• Consequence: GUCA1B NM_002098.6 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.39
• Publications: 4 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 6-42184312-C-T is Benign according to our data. Variant chr6-42184312-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 356717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 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.*503G>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.*503G>A		3_prime_UTR	Exon 4 of 4	ENSP00000230361.3	Q9UMX6

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8748 AN: 152042 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.0686

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.0769

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0676

Gnomad OTH AF: 0.0651

GnomAD4 exome AF: 0.0645 AC: 3375 AN: 52346 Hom.: 125 AF XY: 0.0608 AC XY: 1648 AN XY: 27086

African (AFR) AF: 0.0148 AC: 31 AN: 2100

American (AMR) AF: 0.102 AC: 385 AN: 3766

Ashkenazi Jewish (ASJ) AF: 0.0880 AC: 98 AN: 1114

East Asian (EAS) AF: 0.0568 AC: 187 AN: 3292

South Asian (SAS) AF: 0.0284 AC: 184 AN: 6482

European-Finnish (FIN) AF: 0.0701 AC: 139 AN: 1984

Middle Eastern (MID) AF: 0.0679 AC: 11 AN: 162

European-Non Finnish (NFE) AF: 0.0688 AC: 2115 AN: 30728

Other (OTH) AF: 0.0828 AC: 225 AN: 2718

GnomAD4 genome AF: 0.0575 AC: 8752 AN: 152160 Hom.: 344 Cov.: 32 AF XY: 0.0579 AC XY: 4307 AN XY: 74412

African (AFR) AF: 0.0125 AC: 520 AN: 41548

American (AMR) AF: 0.113 AC: 1731 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3470

East Asian (EAS) AF: 0.0685 AC: 353 AN: 5150

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4826

European-Finnish (FIN) AF: 0.0769 AC: 816 AN: 10610

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.0675 AC: 4591 AN: 67968

Other (OTH) AF: 0.0649 AC: 137 AN: 2112

Alfa AF: 0.0318 Hom.: 22

Bravo AF: 0.0602

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cone dystrophy (1)
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa (1)
-	-	1	Retinitis Pigmentosa, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.5
DANN	Benign	0.88
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs13211352; hg19: chr6-42152050;