rs9875407

Positions:

• chr3-108913648-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005459.4(GUCA1C):​c.442+2479T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,188 control chromosomes in the GnomAD database, including 3,583 homozygotes. 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 0.20 (3583 hom., cov: 32)
• Consequence: GUCA1C NM_005459.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

Genes affected

GUCA1C (HGNC:4680): (guanylate cyclase activator 1C) Predicted to enable calcium ion binding activity and calcium sensitive guanylate cyclase activator activity. Predicted to be involved in signal transduction. Predicted to be located in photoreceptor disc membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCA1C	NM_005459.4	c.442+2479T>G		intron_variant		ENST00000261047.8	NP_005450.3
GUCA1C	NM_001363884.1	c.482+2439T>G		intron_variant			NP_001350813.1
GUCA1C	XM_011513334.3	c.190+2479T>G		intron_variant			XP_011511636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCA1C	ENST00000261047.8	c.442+2479T>G		intron_variant		1	NM_005459.4	ENSP00000261047.3
GUCA1C	ENST00000393963.7	c.482+2439T>G		intron_variant		1		ENSP00000377535.3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30785 AN: 152072 Hom.: 3582 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.202 AC: 30809 AN: 152188 Hom.: 3583 Cov.: 32 AF XY: 0.207 AC XY: 15426 AN XY: 74394

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.204

Alfa AF: 0.229 Hom.: 5169

Bravo AF: 0.199

Asia WGS AF: 0.361 AC: 1253 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs9875407; hg19: chr3-108632495;