1-48742946-G-C

Position:

• chr1-48742946-G-C

Variant summary

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

The ENST00000371833.4(BEND5):​c.746-175C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,088 control chromosomes in the GnomAD database, including 29,932 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 0.59 (29932 hom., cov: 33)
• Consequence: BEND5 ENST00000371833.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

Genes affected

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]

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=-0.27).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEND5	NM_024603.4	c.746-175C>G		intron_variant		ENST00000371833.4	NP_078879.2
AGBL4	NM_032785.4	c.635-79705C>G		intron_variant		ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEND5	ENST00000371833.4	c.746-175C>G		intron_variant		1	NM_024603.4	ENSP00000360899	P1
AGBL4	ENST00000371839.6	c.635-79705C>G		intron_variant		2	NM_032785.4	ENSP00000360905	P1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90207 AN: 151970 Hom.: 29921 Cov.: 33

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.593 AC: 90230 AN: 152088 Hom.: 29932 Cov.: 33 AF XY: 0.584 AC XY: 43397 AN XY: 74350

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.628

Alfa AF: 0.578 Hom.: 1990

Bravo AF: 0.575

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.61

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: rs1934393; hg19: chr1-49208618;