chr3-108913648-A-C

Variant names:

• chr3-108913648-A-C
• rs9875407
• NM_005459.4:c.442+2479T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GUCA1C	NM_005459.4	c.442+2479T>G		intron_variant	Intron 3 of 3	ENST00000261047.8	NP_005450.3
GUCA1C	NM_001363884.1	c.482+2439T>G		intron_variant	Intron 3 of 3		NP_001350813.1
GUCA1C	XM_011513334.3	c.190+2479T>G		intron_variant	Intron 3 of 3		XP_011511636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCA1C	ENST00000261047.8	c.442+2479T>G		intron_variant	Intron 3 of 3	1	NM_005459.4	ENSP00000261047.3
GUCA1C	ENST00000393963.7	c.482+2439T>G		intron_variant	Intron 3 of 3	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

African (AFR) AF: 0.103 AC: 4262 AN: 41560

American (AMR) AF: 0.250 AC: 3820 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 990 AN: 3472

East Asian (EAS) AF: 0.399 AC: 2063 AN: 5174

South Asian (SAS) AF: 0.292 AC: 1409 AN: 4820

European-Finnish (FIN) AF: 0.225 AC: 2380 AN: 10582

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.224 AC: 15213 AN: 67980

Other (OTH) AF: 0.204 AC: 430 AN: 2110

Alfa AF: 0.224 Hom.: 6421

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
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9875407; hg19: chr3-108632495;