rs893184

Variant names:

• chr19-58353113-T-C
• rs893184
• NM_130786.4:c.155A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130786.4(A1BG):​c.155A>G​(p.His52Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.931 in 1,614,066 control chromosomes in the GnomAD database, including 701,710 homozygotes. 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. H52P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.89 (60593 hom., cov: 34)
  • Exomes 𝑓: 0.94 (641117 hom.)
• Consequence: A1BG NM_130786.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 42 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0340167E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
A1BG	NM_130786.4	c.155A>G	p.His52Arg	missense_variant	Exon 3 of 8	ENST00000263100.8	NP_570602.2
A1BG-AS1	NR_015380.2	n.1075+69T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
A1BG	ENST00000263100.8	c.155A>G	p.His52Arg	missense_variant	Exon 3 of 8	1	NM_130786.4	ENSP00000263100.2

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135122 AN: 152132 Hom.: 60581 Cov.: 34

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.900

GnomAD2 exomes AF: 0.904 AC: 227293 AN: 251396 AF XY: 0.910

Gnomad AFR exome AF: 0.757

Gnomad AMR exome AF: 0.809

Gnomad ASJ exome AF: 0.935

Gnomad EAS exome AF: 0.912

Gnomad FIN exome AF: 0.962

Gnomad NFE exome AF: 0.947

Gnomad OTH exome AF: 0.919

GnomAD4 exome AF: 0.935 AC: 1367519 AN: 1461816 Hom.: 641117 Cov.: 83 AF XY: 0.935 AC XY: 679810 AN XY: 727214

African (AFR) AF: 0.745 AC: 24951 AN: 33480

American (AMR) AF: 0.816 AC: 36471 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 24485 AN: 26134

East Asian (EAS) AF: 0.911 AC: 36154 AN: 39700

South Asian (SAS) AF: 0.874 AC: 75379 AN: 86258

European-Finnish (FIN) AF: 0.960 AC: 51205 AN: 53364

Middle Eastern (MID) AF: 0.878 AC: 5065 AN: 5768

European-Non Finnish (NFE) AF: 0.951 AC: 1057957 AN: 1112000

Other (OTH) AF: 0.925 AC: 55852 AN: 60392

GnomAD4 genome AF: 0.888 AC: 135180 AN: 152250 Hom.: 60593 Cov.: 34 AF XY: 0.888 AC XY: 66106 AN XY: 74424

African (AFR) AF: 0.761 AC: 31609 AN: 41524

American (AMR) AF: 0.870 AC: 13311 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3264 AN: 3472

East Asian (EAS) AF: 0.915 AC: 4728 AN: 5166

South Asian (SAS) AF: 0.872 AC: 4203 AN: 4818

European-Finnish (FIN) AF: 0.963 AC: 10229 AN: 10626

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.953 AC: 64821 AN: 68022

Other (OTH) AF: 0.897 AC: 1893 AN: 2110

Alfa AF: 0.929 Hom.: 289532

Bravo AF: 0.874

TwinsUK AF: 0.954 AC: 3539

ALSPAC AF: 0.948 AC: 3654

ESP6500AA AF: 0.774 AC: 3409

ESP6500EA AF: 0.952 AC: 8186

ExAC AF: 0.904 AC: 109823

Asia WGS AF: 0.858 AC: 2987 AN: 3478

EpiCase AF: 0.946

EpiControl AF: 0.944

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0020
DANN	Benign	0.64
DEOGEN2	Benign	0.058	T;T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.10	T;T
MetaRNN	Benign	0.0000010	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.4	N;.
PhyloP100		-1.9
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.5	N;.
REVEL	Benign	0.011
Sift	Benign	0.78	T;.
Sift4G	Benign	1.0	T;.
Vest4		0.011
ClinPred		0.0011	T
GERP RS		-5.2
PromoterAI		0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs893184; hg19: chr19-58864479; COSMIC: COSV54052676; COSMIC: COSV54052676;