NM_032785.4:c.634+94113G>A

Variant names:

• chr1-48773078-C-T
• rs6664435
• NM_032785.4:c.634+94113G>A

Variant summary

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

The NM_032785.4(AGBL4):​c.634+94113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 151,956 control chromosomes in the GnomAD database, including 37,025 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 (37025 hom., cov: 31)
• Consequence: AGBL4 NM_032785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• Publications: 5 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]

BEND5 (HGNC:25668): (BEN domain containing 5) Predicted to enable DNA binding activity. Involved in negative regulation of transcription, DNA-templated. Predicted to be located in Golgi apparatus. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032785.4. 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.634+94113G>A		intron	N/A	NP_116174.3
	BEND5	NM_024603.4	MANE Select	c.226+3528G>A		intron	N/A	NP_078879.2
	BEND5	NM_001349795.2		c.-48G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 8	NP_001336724.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGBL4	ENST00000371839.6	TSL:2 MANE Select	c.634+94113G>A		intron	N/A	ENSP00000360905.1
	BEND5	ENST00000371833.4	TSL:1 MANE Select	c.226+3528G>A		intron	N/A	ENSP00000360899.3
	AGBL4	ENST00000416121.5	TSL:1	c.169+94113G>A		intron	N/A	ENSP00000401622.1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105308 AN: 151838 Hom.: 37001 Cov.: 31

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.693 AC: 105378 AN: 151956 Hom.: 37025 Cov.: 31 AF XY: 0.686 AC XY: 50923 AN XY: 74272

African (AFR) AF: 0.748 AC: 30989 AN: 41452

American (AMR) AF: 0.683 AC: 10430 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2489 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1536 AN: 5132

South Asian (SAS) AF: 0.539 AC: 2587 AN: 4800

European-Finnish (FIN) AF: 0.671 AC: 7087 AN: 10564

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48018 AN: 67954

Other (OTH) AF: 0.689 AC: 1451 AN: 2106

Alfa AF: 0.703 Hom.: 60521

Bravo AF: 0.697

Asia WGS AF: 0.428 AC: 1490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0070
DANN	Benign	0.66
PhyloP100		-2.6
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: rs6664435; hg19: chr1-49238750;