Genetic Variant NM_130786.4:c.1217G>A (chr19-58347616-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_130786.4(A1BG):c.1217G>A(p.Arg406Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000755 in 1,323,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

A1BG
NM_130786.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.50

Publications

0 publications found

Variant links:

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 links:

ENSG00000268230 (HGNC:):

ENSG00000268230 links:

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

A1BG-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047284365).

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.1217G>A	p.Arg406Gln	missense	Exon 7 of 8	NP_570602.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
A1BG	ENST00000263100.8	TSL:1 MANE Select	c.1217G>A	p.Arg406Gln	missense	Exon 7 of 8	ENSP00000263100.2	P04217-1
A1BG	ENST00000598345.2	TSL:1	c.-271G>A		5_prime_UTR	Exon 1 of 2	ENSP00000521034.1	A0ABJ7H347
A1BG	ENST00000596924.1	TSL:1	n.19G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.55e-7

AC:

AN:

1323956

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

648592

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27996

American (AMR)

AF:

0.00

AC:

AN:

27716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21174

East Asian (EAS)

AF:

0.00

AC:

AN:

32852

South Asian (SAS)

AF:

0.00

AC:

AN:

71198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4894

European-Non Finnish (NFE)

AF:

9.52e-7

AC:

AN:

1049970

Other (OTH)

AF:

0.00

AC:

AN:

55012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.0

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.53

M_CAP

Benign

0.011

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

PhyloP100

-3.5

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.35

REVEL

Benign

0.013

Sift

Benign

0.48

Sift4G

Benign

0.45

Polyphen

0.32

Vest4

0.11

MutPred

0.32

Loss of MoRF binding (P = 0.0259)

MVP

0.20

MPC

0.40

ClinPred

0.11

GERP RS

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.27

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over