rs737575

Variant names:

• chr13-51035204-A-G
• rs737575
• ENST00000493639.6:n.226-1045T>C

Variant summary

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

The ENST00000493639.6(GUCY1B2):​n.226-1045T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 152,260 control chromosomes in the GnomAD database, including 267 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 0.043 (267 hom., cov: 33)
• Consequence: GUCY1B2 ENST00000493639.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000493639.6. 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
	GUCY1B2	NR_003923.2		n.377-1045T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1B2	ENST00000493639.6	TSL:1	n.226-1045T>C		intron	N/A
	GUCY1B2	ENST00000389600.6	TSL:5	n.427-5511T>C		intron	N/A
	GUCY1B2	ENST00000531898.5	TSL:6	n.170-1045T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0426 AC: 6484 AN: 152142 Hom.: 257 Cov.: 33

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0701

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00914

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0428 AC: 6515 AN: 152260 Hom.: 267 Cov.: 33 AF XY: 0.0473 AC XY: 3518 AN XY: 74436

African (AFR) AF: 0.0612 AC: 2542 AN: 41546

American (AMR) AF: 0.103 AC: 1579 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.122 AC: 630 AN: 5182

South Asian (SAS) AF: 0.0701 AC: 338 AN: 4820

European-Finnish (FIN) AF: 0.0630 AC: 668 AN: 10608

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00914 AC: 622 AN: 68030

Other (OTH) AF: 0.0430 AC: 91 AN: 2114

Alfa AF: 0.0317 Hom.: 18

Bravo AF: 0.0484

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.62
PhyloP100		-1.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs737575;

hg19: chr13-51609340;