rs7325866

Variant names:

• chr13-51034649-C-T
• rs7325866
• ENST00000493639.6:n.226-490G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000493639.6(GUCY1B2):​n.226-490G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.065 in 152,208 control chromosomes in the GnomAD database, including 602 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 0.065 (602 hom., cov: 32)
• Consequence: GUCY1B2 ENST00000493639.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 1 publications found

Genes affected

GUCY1B2 (HGNC:):

GUCY1B2 (HGNC:4686): (guanylate cyclase 1 soluble subunit beta 2 (pseudogene)) Predicted to enable several functions, including GTP binding activity; guanylate cyclase activity; and heme binding activity. Predicted to be involved in cGMP-mediated signaling. Predicted to be located in cytoplasm. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1B2	NR_003923.2	n.377-490G>A		intron_variant	Intron 3 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY1B2	ENST00000493639.6	n.226-490G>A		intron_variant	Intron 3 of 16	1
GUCY1B2	ENST00000389600.6	n.427-4956G>A		intron_variant	Intron 3 of 9	5
GUCY1B2	ENST00000531898.5	n.170-490G>A		intron_variant	Intron 2 of 12	6

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9843 AN: 152088 Hom.: 585 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00981

Gnomad OTH AF: 0.0607

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

GnomAD4 genome AF: 0.0650 AC: 9886 AN: 152208 Hom.: 602 Cov.: 32 AF XY: 0.0684 AC XY: 5086 AN XY: 74400

African (AFR) AF: 0.135 AC: 5623 AN: 41514

American (AMR) AF: 0.114 AC: 1738 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3468

East Asian (EAS) AF: 0.121 AC: 628 AN: 5188

South Asian (SAS) AF: 0.0739 AC: 356 AN: 4816

European-Finnish (FIN) AF: 0.0629 AC: 667 AN: 10600

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00981 AC: 667 AN: 68012

Other (OTH) AF: 0.0624 AC: 132 AN: 2116

Alfa AF: 0.0348 Hom.: 434

Bravo AF: 0.0726

Asia WGS AF: 0.108 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.62
PhyloP100		0.29

Splicing

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

Other links and lift over

dbSNP: rs7325866; hg19: chr13-51608785;