chr4-155796434-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I301V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GUCY1B1 NM_000857.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.06
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000857.5. 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
	GUCY1B1	NM_000857.5	MANE Select	c.901A>T	p.Ile301Phe	missense	Exon 8 of 14	NP_000848.1	Q02153-1
	GUCY1B1	NM_001291951.3		c.967A>T	p.Ile323Phe	missense	Exon 9 of 15	NP_001278880.1	E9PCN2
	GUCY1B1	NM_001291952.3		c.841A>T	p.Ile281Phe	missense	Exon 9 of 15	NP_001278881.1	Q02153-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY1B1	ENST00000264424.13	TSL:1 MANE Select	c.901A>T	p.Ile301Phe	missense	Exon 8 of 14	ENSP00000264424.8	Q02153-1
	GUCY1B1	ENST00000507146.5	TSL:1	c.697A>T	p.Ile233Phe	missense	Exon 9 of 15	ENSP00000422313.1	D6RC99
	GUCY1B1	ENST00000503520.5	TSL:1	c.901A>T	p.Ile301Phe	missense	Exon 8 of 14	ENSP00000420842.1	Q02153-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	0.0029	D
MutationAssessor	Benign	1.5	L
PhyloP100		7.1
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.66	N
REVEL	Uncertain	0.57
Sift	Benign	0.69	T
Sift4G	Benign	0.70	T
Polyphen		0.38	B
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
Mutation Taster		=43/57	disease causing

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

Other links and lift over

dbSNP: rs201359483; hg19: chr4-156717586;