20-5922677-G-T

Variant names:

• chr20-5922677-G-T
• rs910122
• NM_001819.3:c.533G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001819.3(CHGB):​c.533G>T​(p.Arg178Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R178Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CHGB NM_001819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

Genes affected

CHGB (HGNC:1930): (chromogranin B) This gene encodes a tyrosine-sulfated secretory protein abundant in peptidergic endocrine cells and neurons. This protein may serve as a precursor for regulatory peptides. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046386957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHGB	NM_001819.3	c.533G>T	p.Arg178Leu	missense_variant	Exon 4 of 5	ENST00000378961.9	NP_001810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHGB	ENST00000378961.9	c.533G>T	p.Arg178Leu	missense_variant	Exon 4 of 5	1	NM_001819.3	ENSP00000368244.4
CHGB	ENST00000455042.1	c.473G>T	p.Arg158Leu	missense_variant	Exon 5 of 5	3		ENSP00000416643.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461758 Hom.: 0 Cov.: 67 AF XY: 0.00000138 AC XY: 1 AN XY: 727148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.0020
DANN	Benign	0.64
DEOGEN2	Benign	0.086	T;T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.046	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.16	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.042
Sift	Benign	0.059	T;T
Sift4G	Benign	0.096	T;T
Polyphen		0.0	B;.
Vest4		0.10
MutPred		0.36		Loss of methylation at K175 (P = 0.1509);.;
MVP		0.11
MPC		0.13
ClinPred		0.12	T
GERP RS		-11
Varity_R		0.061
gMVP		0.11

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: rs910122; hg19: chr20-5903323; COSMIC: COSV66760629; COSMIC: COSV66760629;