rs193921115

Positions:

• chr1-48727942-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024603.4(BEND5):​c.1210A>G​(p.Ile404Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BEND5 NM_024603.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.63

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]

BEND5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41223893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEND5	NM_024603.4	c.1210A>G	p.Ile404Val	missense_variant	6/6	ENST00000371833.4	NP_078879.2
AGBL4	NM_032785.4	c.635-64701A>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.1210A>G	p.Ile404Val	missense_variant	6/6	1	NM_024603.4	ENSP00000360899.3
AGBL4	ENST00000371839.6	c.635-64701A>G		intron_variant		2	NM_032785.4	ENSP00000360905.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.058	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.90	L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.25
Sift	Uncertain	0.018	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.90	P
Vest4		0.47
MutPred		0.12		Gain of MoRF binding (P = 0.1007);
MVP		0.54
MPC		0.76
ClinPred		0.87	D
GERP RS		5.8
Varity_R		0.16
gMVP		0.29

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: rs193921115; hg19: chr1-49193614; COSMIC: COSV65716788;