chr1-48831821-T-A

Variant names:

• chr1-48831821-T-A
• rs1934404
• NM_032785.4:c.634+35370A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032785.4(AGBL4):​c.634+35370A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,198 control chromosomes in the GnomAD database, including 2,717 homozygotes. 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: 𝑓 0.17 (2717 hom., cov: 32)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803
• Publications: 1 publications found

Genes affected

AGBL4 (HGNC:25892): (AGBL carboxypeptidase 4) Predicted to enable metallocarboxypeptidase activity and tubulin binding activity. Predicted to be involved in C-terminal protein deglutamylation; defense response to virus; and protein side chain deglutamylation. Predicted to act upstream of or within several processes, including axonal transport of mitochondrion; positive regulation of ubiquitin-dependent protein catabolic process; and regulation of blastocyst development. Located in Golgi apparatus; centriole; and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.634+35370A>T		intron_variant	Intron 6 of 13	ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.634+35370A>T		intron_variant	Intron 6 of 13	2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000416121.5	c.169+35370A>T		intron_variant	Intron 2 of 6	1		ENSP00000401622.1
AGBL4	ENST00000371836.1	c.635-13599A>T		intron_variant	Intron 6 of 6	1		ENSP00000360902.1
AGBL4	ENST00000371838.5	c.634+35370A>T		intron_variant	Intron 6 of 8	5		ENSP00000360904.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25465 AN: 152080 Hom.: 2723 Cov.: 32

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.181

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.167 AC: 25458 AN: 152198 Hom.: 2717 Cov.: 32 AF XY: 0.171 AC XY: 12709 AN XY: 74394

African (AFR) AF: 0.0533 AC: 2216 AN: 41556

American (AMR) AF: 0.209 AC: 3201 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 685 AN: 3472

East Asian (EAS) AF: 0.415 AC: 2136 AN: 5150

South Asian (SAS) AF: 0.284 AC: 1366 AN: 4816

European-Finnish (FIN) AF: 0.158 AC: 1672 AN: 10600

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13466 AN: 67992

Other (OTH) AF: 0.181 AC: 384 AN: 2116

Alfa AF: 0.177 Hom.: 353

Bravo AF: 0.166

Asia WGS AF: 0.311 AC: 1077 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		0.80
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: rs1934404; hg19: chr1-49297493;