1-49849680-A-G

Position:

• chr1-49849680-A-G

Variant summary

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

The NM_032785.4(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_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.157+1716T>C		intron_variant		ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.157+1716T>C		intron_variant		2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000371836.1	c.157+1716T>C		intron_variant		1		ENSP00000360902.1
AGBL4	ENST00000371838.5	c.157+1716T>C		intron_variant		5		ENSP00000360904.1
AGBL4	ENST00000497451.1	n.123+1716T>C		intron_variant		2

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

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.696

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.76

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: rs6693846; hg19: chr1-50315352;