1-44785227-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153274.3(BEST4):​c.793G>A​(p.Ala265Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

BEST4
NM_153274.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0780
Variant links:
Genes affected
BEST4 (HGNC:17106): (bestrophin 4) This gene is a member of the bestrophin gene family of anion channels. Bestrophin genes share a similar gene structure with highly conserved exon-intron boundaries, but with distinct 3' ends. Bestrophins are transmembrane proteins that contain a homologous region rich in aromatic residues, including an invariant arg-phe-pro motif. Mutation in one of the family members (bestrophin 1) is associated with vitelliform macular dystrophy. The bestrophin 4 gene is predominantly expressed in the colon. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06784716).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BEST4NM_153274.3 linkc.793G>A p.Ala265Thr missense_variant Exon 6 of 9 ENST00000372207.4 NP_695006.1 Q8NFU0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BEST4ENST00000372207.4 linkc.793G>A p.Ala265Thr missense_variant Exon 6 of 9 1 NM_153274.3 ENSP00000361281.3 Q8NFU0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.793G>A (p.A265T) alteration is located in exon 6 (coding exon 6) of the BEST4 gene. This alteration results from a G to A substitution at nucleotide position 793, causing the alanine (A) at amino acid position 265 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
6.3
DANN
Benign
0.76
DEOGEN2
Benign
0.29
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.068
T
MetaSVM
Uncertain
0.042
D
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.48
N
REVEL
Benign
0.22
Sift
Benign
0.61
T
Sift4G
Benign
0.59
T
Polyphen
0.0010
B
Vest4
0.077
MutPred
0.36
Gain of phosphorylation at A265 (P = 0.0152);
MVP
0.47
MPC
0.82
ClinPred
0.017
T
GERP RS
1.9
Varity_R
0.033
gMVP
0.45

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1651176198; hg19: chr1-45250899; API