4-155796434-A-T

Variant names:

• chr4-155796434-A-T
• rs201359483
• NM_000857.5:c.901A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000857.5(GUCY1B1):​c.901A>T​(p.Ile301Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GUCY1B1 NM_000857.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.06

Genes affected

GUCY1B1 (HGNC:4687): (guanylate cyclase 1 soluble subunit beta 1) This gene encodes the beta subunit of the soluble guanylate cyclase (sGC), which catalyzes the conversion of GTP (guanosine triphosphate) to cGMP (cyclic guanosine monophosphate). The encoded protein contains an HNOX domain, which serves as a receptor for ligands such as nitric oxide, oxygen and nitrovasodilator drugs. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1B1	NM_000857.5	c.901A>T	p.Ile301Phe	missense_variant	Exon 8 of 14	ENST00000264424.13	NP_000848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY1B1	ENST00000264424.13	c.901A>T	p.Ile301Phe	missense_variant	Exon 8 of 14	1	NM_000857.5	ENSP00000264424.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.30	T;.;.;.;T;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	.;D;D;D;D;D;D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.67	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.0029	D
MutationAssessor	Benign	1.5	.;.;.;.;L;L;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.66	N;N;N;N;N;N;N
REVEL	Uncertain	0.57
Sift	Benign	0.69	T;T;T;T;T;T;T
Sift4G	Benign	0.70	T;T;T;T;T;T;T
Polyphen		0.38, 0.83, 0.45, 0.65	.;B;.;P;B;P;.
Vest4		0.82
MutPred		0.60		.;Loss of catalytic residue at L328 (P = 0.0319);.;.;.;.;.;
MVP		0.96
MPC		1.2
ClinPred		0.83	D
GERP RS		5.6
Varity_R		0.23
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs201359483; hg19: chr4-156717586;