rs2103266

Variant names:

• chr1-49556701-G-A
• rs2103266
• NM_032785.4:c.282+140612C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-49556701-G-A
• chr1-49556701-G-C

Variant summary

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

The NM_032785.4(AGBL4):​c.282+140612C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,746 control chromosomes in the GnomAD database, including 22,213 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 0.52 (22213 hom., cov: 30)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 0 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGBL4	NM_032785.4	c.282+140612C>T		intron_variant	Intron 3 of 13	ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGBL4	ENST00000371839.6	c.282+140612C>T		intron_variant	Intron 3 of 13	2	NM_032785.4	ENSP00000360905.1
AGBL4	ENST00000371836.1	c.282+140612C>T		intron_variant	Intron 3 of 6	1		ENSP00000360902.1
AGBL4	ENST00000371838.5	c.282+140612C>T		intron_variant	Intron 3 of 8	5		ENSP00000360904.1
AGBL4	ENST00000497451.1	n.249-29097C>T		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79461 AN: 151630 Hom.: 22210 Cov.: 30

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.524 AC: 79487 AN: 151746 Hom.: 22213 Cov.: 30 AF XY: 0.521 AC XY: 38610 AN XY: 74166

African (AFR) AF: 0.352 AC: 14578 AN: 41414

American (AMR) AF: 0.593 AC: 9050 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2229 AN: 3460

East Asian (EAS) AF: 0.213 AC: 1088 AN: 5104

South Asian (SAS) AF: 0.489 AC: 2341 AN: 4792

European-Finnish (FIN) AF: 0.584 AC: 6165 AN: 10552

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.621 AC: 42132 AN: 67868

Other (OTH) AF: 0.558 AC: 1172 AN: 2100

Alfa AF: 0.565 Hom.: 3124

Bravo AF: 0.518

Asia WGS AF: 0.337 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.3
DANN	Benign	0.61
PhyloP100		0.14
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: rs2103266; hg19: chr1-50022373;