19-58350428-G-A

Variant names:

• chr19-58350428-G-A
• rs757556359
• NM_130786.4:c.1134C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_130786.4(A1BG):​c.1134C>T​(p.Asp378Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: A1BG NM_130786.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=1.57 with no splicing effect.

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.1134C>T	p.Asp378Asp	synonymous	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.1134C>T	p.Asp378Asp	synonymous	Exon 6 of 8	ENSP00000263100.2	P04217-1
	ENSG00000268230	ENST00000600123.5	TSL:1	n.1243C>T		non_coding_transcript_exon	Exon 6 of 8
	A1BG	ENST00000850949.1		c.1134C>T	p.Asp378Asp	synonymous	Exon 6 of 8	ENSP00000521032.1	A0ABJ7H345

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398906 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690146

African (AFR) AF: 0.00 AC: 0 AN: 31630

American (AMR) AF: 0.0000279 AC: 1 AN: 35886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25158

East Asian (EAS) AF: 0.00 AC: 0 AN: 35814

South Asian (SAS) AF: 0.00 AC: 0 AN: 79336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079380

Other (OTH) AF: 0.00 AC: 0 AN: 58014

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.0
DANN	Benign	0.93
PhyloP100		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs757556359; hg19: chr19-58861794;