rs893184

Positions:

• chr19-58353113-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000263100.8(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. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.89 (60593 hom., cov: 34)
  • Exomes 𝑓: 0.94 (641117 hom.)
• Consequence: A1BG ENST00000263100.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

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]

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
A1BG	NM_130786.4	c.155A>G	p.His52Arg	missense_variant	3/8	ENST00000263100.8	NP_570602.2
A1BG-AS1	NR_015380.2	n.1075+69T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
A1BG	ENST00000263100.8	c.155A>G	p.His52Arg	missense_variant	3/8	1	NM_130786.4	ENSP00000263100	P1
A1BG-AS1	ENST00000670460.1	n.128-601T>C		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.904 AC: 227293 AN: 251396 Hom.: 103327 AF XY: 0.910 AC XY: 123691 AN XY: 135898

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 SAS exome AF: 0.871

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

Gnomad4 AFR exome AF: 0.745

Gnomad4 AMR exome AF: 0.816

Gnomad4 ASJ exome AF: 0.937

Gnomad4 EAS exome AF: 0.911

Gnomad4 SAS exome AF: 0.874

Gnomad4 FIN exome AF: 0.960

Gnomad4 NFE exome AF: 0.951

Gnomad4 OTH exome AF: 0.925

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

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.915

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.953

Gnomad4 OTH AF: 0.897

Alfa AF: 0.934 Hom.: 141590

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;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.5	N;.
REVEL	Benign	0.011
Sift	Benign	0.78	T;.
Sift4G	Benign	1.0	T;.
Polyphen		0.0	B;.
Vest4		0.011
MPC		0.38
ClinPred		0.0011	T
GERP RS		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.13

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