19-58350624-G-C

Variant names:

• chr19-58350624-G-C
• rs1038758891
• NM_130786.4:c.938C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130786.4(A1BG):​c.938C>G​(p.Pro313Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000781 in 1,280,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P313L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: A1BG NM_130786.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07670331).

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.938C>G	p.Pro313Arg	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.938C>G	p.Pro313Arg	missense	Exon 6 of 8	ENSP00000263100.2	P04217-1
	ENSG00000268230	ENST00000600123.5	TSL:1	n.1047C>G		non_coding_transcript_exon	Exon 6 of 8
	A1BG	ENST00000850949.1		c.938C>G	p.Pro313Arg	missense	Exon 6 of 8	ENSP00000521032.1	A0ABJ7H345

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.81e-7 AC: 1 AN: 1280102 Hom.: 0 Cov.: 30 AF XY: 0.00000160 AC XY: 1 AN XY: 624072

African (AFR) AF: 0.00 AC: 0 AN: 24570

American (AMR) AF: 0.00 AC: 0 AN: 17240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18538

East Asian (EAS) AF: 0.00 AC: 0 AN: 30726

South Asian (SAS) AF: 0.00 AC: 0 AN: 62314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3750

European-Non Finnish (NFE) AF: 9.72e-7 AC: 1 AN: 1028710

Other (OTH) AF: 0.00 AC: 0 AN: 52500

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.14
Sift	Uncertain	0.011	D
Sift4G	Benign	0.22	T
Polyphen		0.0030	B
Vest4		0.075
MutPred		0.41		Loss of glycosylation at P313 (P = 0.0372)
MVP		0.35
MPC		0.47
ClinPred		0.11	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.29
Mutation Taster		=97/3	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: rs1038758891; hg19: chr19-58861990;