chr19-58350571-C-T

Variant names:

• chr19-58350571-C-T
• rs1439769564
• NM_130786.4:c.991G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_130786.4(A1BG):​c.991G>A​(p.Gly331Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,372,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. G331C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: A1BG NM_130786.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773
• Publications: 0 publications found

Genes affected

A1BG (HGNC:5): (alpha-1-B glycoprotein) The protein encoded by this gene is a plasma glycoprotein of unknown function. The protein shows sequence similarity to the variable regions of some immunoglobulin supergene family member proteins. [provided by RefSeq, Jul 2008]

ENSG00000268230 (HGNC:):

A1BG-AS1 (HGNC:37133): (A1BG antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26805806).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130786.4. 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
	A1BG	NM_130786.4	MANE Select	c.991G>A	p.Gly331Ser	missense	Exon 6 of 8	NP_570602.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	A1BG	ENST00000263100.8	TSL:1 MANE Select	c.991G>A	p.Gly331Ser	missense	Exon 6 of 8	ENSP00000263100.2	P04217-1
	ENSG00000268230	ENST00000600123.5	TSL:1	n.1100G>A		non_coding_transcript_exon	Exon 6 of 8
	A1BG	ENST00000850949.1		c.991G>A	p.Gly331Ser	missense	Exon 6 of 8	ENSP00000521032.1	A0ABJ7H345

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1372140 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 675184

African (AFR) AF: 0.00 AC: 0 AN: 28820

American (AMR) AF: 0.00 AC: 0 AN: 32220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24270

East Asian (EAS) AF: 0.00 AC: 0 AN: 34038

South Asian (SAS) AF: 0.00 AC: 0 AN: 76590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5004

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1067276

Other (OTH) AF: 0.00 AC: 0 AN: 56698

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.77
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.013
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.21
MutPred		0.33		Gain of phosphorylation at G331 (P = 0.041)
MVP		0.34
MPC		1.0
ClinPred		0.70	D
GERP RS		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.49
Mutation Taster		=95/5	polymorphism

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: rs1439769564; hg19: chr19-58861937;