chr6-68956768-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001704.3(ADGRB3):c.1484C>T(p.Thr495Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,461,660 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000039 ( 1 hom. )
Consequence
ADGRB3
NM_001704.3 missense
NM_001704.3 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: 1.47
Genes affected
ADGRB3 (HGNC:945): (adhesion G protein-coupled receptor B3) This p53-target gene encodes a brain-specific angiogenesis inhibitor, a seven-span transmembrane protein, and is thought to be a member of the secretin receptor family. Brain-specific angiogenesis proteins BAI2 and BAI3 are similar to BAI1 in structure, have similar tissue specificities, and may also play a role in angiogenesis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.23091146).
BS2
High AC in GnomAdExome4 at 57 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRB3 | NM_001704.3 | c.1484C>T | p.Thr495Met | missense_variant | 8/32 | ENST00000370598.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRB3 | ENST00000370598.6 | c.1484C>T | p.Thr495Met | missense_variant | 8/32 | 1 | NM_001704.3 | P1 | |
ADGRB3 | ENST00000546190.5 | c.1484C>T | p.Thr495Met | missense_variant | 6/30 | 1 | P1 | ||
ADGRB3 | ENST00000684661.1 | c.1484C>T | p.Thr495Met | missense_variant, NMD_transcript_variant | 8/32 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251234Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135766
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GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461660Hom.: 1 Cov.: 33 AF XY: 0.0000385 AC XY: 28AN XY: 727116
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 26, 2022 | The c.1484C>T (p.T495M) alteration is located in exon 8 (coding exon 6) of the ADGRB3 gene. This alteration results from a C to T substitution at nucleotide position 1484, causing the threonine (T) at amino acid position 495 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Benign
D;.
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at