rs12086219

Positions:

• chr1-48755631-G-A
• chr1-48755631-G-C

Variant summary

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

The ENST00000371833.4(BEND5):​c.745+3269C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 152,190 control chromosomes in the GnomAD database, including 699 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 0.081 (699 hom., cov: 32)
• Consequence: BEND5 ENST00000371833.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEND5	NM_024603.4	c.745+3269C>T		intron_variant		ENST00000371833.4	NP_078879.2
AGBL4	NM_032785.4	c.635-92390C>T		intron_variant		ENST00000371839.6	NP_116174.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEND5	ENST00000371833.4	c.745+3269C>T		intron_variant		1	NM_024603.4	ENSP00000360899	P1
AGBL4	ENST00000371839.6	c.635-92390C>T		intron_variant		2	NM_032785.4	ENSP00000360905	P1

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12381 AN: 152072 Hom.: 691 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.0804

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0665

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

GnomAD4 genome AF: 0.0815 AC: 12403 AN: 152190 Hom.: 699 Cov.: 32 AF XY: 0.0822 AC XY: 6114 AN XY: 74404

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.0797

Gnomad4 FIN AF: 0.0345

Gnomad4 NFE AF: 0.0400

Gnomad4 OTH AF: 0.0668

Alfa AF: 0.0734 Hom.: 84

Bravo AF: 0.0933

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.78

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: rs12086219; hg19: chr1-49221303;