20-5911680-C-G

Variant names:

• chr20-5911680-C-G
• rs1008938086
• NM_001819.3:c.47C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001819.3(CHGB):​c.47C>G​(p.Ala16Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000759 in 1,317,100 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. A16V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CHGB NM_001819.3 missense, splice_region
• Scores: Splicing: ADA: 0.6925
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 0 publications found

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

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_001819.3. 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
	CHGB	NM_001819.3	MANE Select	c.47C>G	p.Ala16Gly	missense splice_region	Exon 1 of 5	NP_001810.2	P05060

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHGB	ENST00000378961.9	TSL:1 MANE Select	c.47C>G	p.Ala16Gly	missense splice_region	Exon 1 of 5	ENSP00000368244.4	P05060
	CHGB	ENST00000966395.1		c.47C>G	p.Ala16Gly	missense splice_region	Exon 1 of 5	ENSP00000636454.1
	CHGB	ENST00000886261.1		c.47C>G	p.Ala16Gly	missense splice_region	Exon 1 of 5	ENSP00000556320.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000161 AC: 1 AN: 62036 AF XY: 0.0000283

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000735

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.59e-7 AC: 1 AN: 1317100 Hom.: 0 Cov.: 30 AF XY: 0.00000154 AC XY: 1 AN XY: 647318

African (AFR) AF: 0.00 AC: 0 AN: 26252

American (AMR) AF: 0.0000393 AC: 1 AN: 25466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21796

East Asian (EAS) AF: 0.00 AC: 0 AN: 28540

South Asian (SAS) AF: 0.00 AC: 0 AN: 71160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4476

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1047994

Other (OTH) AF: 0.00 AC: 0 AN: 54600

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.56
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0052	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.1
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.13
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.027	D
Polyphen		1.0	D
Vest4		0.27
MutPred		0.71		Loss of sheet (P = 0.1158)
MVP		0.60
MPC		0.46
ClinPred		0.72	D
GERP RS		3.3
PromoterAI		-0.16	Neutral
Varity_R		0.14
gMVP		0.19
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.69
dbscSNV1_RF	Benign	0.62
SpliceAI score (max)		0.070		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: rs1008938086; hg19: chr20-5892326;