1-48970435-T-C

Variant names:

• chr1-48970435-T-C
• rs17105335
• NM_032785.4:c.594+75149A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032785.4(AGBL4):​c.594+75149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 152,236 control chromosomes in the GnomAD database, including 252 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 0.056 (252 hom., cov: 32)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.594+75149A>G		intron_variant	Intron 5 of 13	ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.594+75149A>G		intron_variant	Intron 5 of 13	2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000416121.5	c.129+75149A>G		intron_variant	Intron 1 of 6	1		ENSP00000401622.1
AGBL4	ENST00000371836.1	c.594+75149A>G		intron_variant	Intron 5 of 6	1		ENSP00000360902.1
AGBL4	ENST00000371838.5	c.594+75149A>G		intron_variant	Intron 5 of 8	5		ENSP00000360904.1

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8561 AN: 152118 Hom.: 249 Cov.: 32

Gnomad AFR AF: 0.0633

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0744

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.0473

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

GnomAD4 genome AF: 0.0563 AC: 8574 AN: 152236 Hom.: 252 Cov.: 32 AF XY: 0.0567 AC XY: 4222 AN XY: 74430

Gnomad4 AFR AF: 0.0634

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0742

Gnomad4 SAS AF: 0.0483

Gnomad4 FIN AF: 0.0674

Gnomad4 NFE AF: 0.0538

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0553 Hom.: 302

Bravo AF: 0.0546

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.85

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: rs17105335; hg19: chr1-49436107;