1-49849680-A-G

Variant names:

• chr1-49849680-A-G
• rs6693846
• NM_032785.4:c.157+1716T>C

Variant summary

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

The NM_001323574.2(AGBL4):​c.157+1716T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 151,816 control chromosomes in the GnomAD database, including 36,563 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 0.69 (36563 hom., cov: 30)
• Consequence: AGBL4 NM_001323574.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323574.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	NM_032785.4	MANE Select	c.157+1716T>C		intron	N/A	NP_116174.3
	AGBL4	NM_001323574.2		c.157+1716T>C		intron	N/A	NP_001310503.1
	AGBL4	NM_001323573.2		c.157+1716T>C		intron	N/A	NP_001310502.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	ENST00000371839.6	TSL:2 MANE Select	c.157+1716T>C		intron	N/A	ENSP00000360905.1
	AGBL4	ENST00000371836.1	TSL:1	c.157+1716T>C		intron	N/A	ENSP00000360902.1
	AGBL4	ENST00000371838.5	TSL:5	c.157+1716T>C		intron	N/A	ENSP00000360904.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104156 AN: 151700 Hom.: 36526 Cov.: 30

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.687 AC: 104245 AN: 151816 Hom.: 36563 Cov.: 30 AF XY: 0.680 AC XY: 50417 AN XY: 74180

African (AFR) AF: 0.785 AC: 32541 AN: 41438

American (AMR) AF: 0.681 AC: 10371 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2630 AN: 3468

East Asian (EAS) AF: 0.274 AC: 1414 AN: 5158

South Asian (SAS) AF: 0.549 AC: 2643 AN: 4818

European-Finnish (FIN) AF: 0.618 AC: 6473 AN: 10474

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45920 AN: 67910

Other (OTH) AF: 0.696 AC: 1468 AN: 2110

Alfa AF: 0.610 Hom.: 2379

Bravo AF: 0.697

Asia WGS AF: 0.445 AC: 1550 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.76
PhyloP100		-0.084
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: rs6693846; hg19: chr1-50315352;