NM_000857.5:c.1486A>G

Variant names:

• chr4-155803696-A-G
• rs368196119
• NM_000857.5:c.1486A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000857.5(GUCY1B1):​c.1486A>G​(p.Ile496Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,452,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: GUCY1B1 NM_000857.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.49

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27250034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY1B1	NM_000857.5	c.1486A>G	p.Ile496Val	missense_variant	Exon 11 of 14	ENST00000264424.13	NP_000848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY1B1	ENST00000264424.13	c.1486A>G	p.Ile496Val	missense_variant	Exon 11 of 14	1	NM_000857.5	ENSP00000264424.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000510 AC: 12 AN: 235232 Hom.: 0 AF XY: 0.0000787 AC XY: 10 AN XY: 127054

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000353

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000937

Gnomad OTH exome AF: 0.000175

GnomAD4 exome AF: 0.0000124 AC: 18 AN: 1452408 Hom.: 0 Cov.: 29 AF XY: 0.0000180 AC XY: 13 AN XY: 721676

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.0000377

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000189

ExAC AF: 0.0000911 AC: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.016	T;.;.;.;T;.;T
Eigen	Benign	-0.011
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	.;D;D;D;D;D;D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.27	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.66	.;.;.;.;N;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.67	N;N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.58	T;T;T;T;T;T;T
Sift4G	Benign	0.49	T;T;T;T;T;T;T
Polyphen		0.0010, 0.0020, 0.0, 0.0050	.;B;.;B;B;B;.
Vest4		0.42
MVP		0.65
MPC		0.57
ClinPred		0.17	T
GERP RS		5.6
Varity_R		0.20
gMVP		0.86

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: rs368196119; hg19: chr4-156724848;