chr19-19182679-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001145784.2(BORCS8):c.220G>A(p.Val74Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,549,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000093 ( 0 hom. )
Consequence
BORCS8
NM_001145784.2 missense
NM_001145784.2 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: 2.99
Genes affected
BORCS8 (HGNC:37247): (BLOC-1 related complex subunit 8) Involved in heart development. Part of BORC complex. [provided by Alliance of Genome Resources, Apr 2022]
MEF2B (HGNC:6995): (myocyte enhancer factor 2B) The product of this gene is a member of the MADS/MEF2 family of DNA binding proteins. The protein is thought to regulate gene expression, including expression of the smooth muscle myosin heavy chain gene. This region undergoes considerable alternative splicing, with transcripts supporting two non-overlapping loci (GeneID 729991 and 100271849) as well as numerous read-through transcripts that span both loci (annotated as GeneID 4207). Several isoforms of this protein are expressed from either this locus or from some of the read-through transcripts annotated on GeneID 4207. [provided by RefSeq, Jan 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
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=0.4082269).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BORCS8 | NM_001145784.2 | c.220G>A | p.Val74Met | missense_variant | 4/6 | ENST00000462790.8 | |
BORCS8-MEF2B | NR_027308.2 | n.255G>A | non_coding_transcript_exon_variant | 4/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BORCS8 | ENST00000462790.8 | c.220G>A | p.Val74Met | missense_variant | 4/6 | 1 | NM_001145784.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152062Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
3
AN:
152062
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000663 AC: 1AN: 150782Hom.: 0 AF XY: 0.0000125 AC XY: 1AN XY: 80184
GnomAD3 exomes
AF:
AC:
1
AN:
150782
Hom.:
AF XY:
AC XY:
1
AN XY:
80184
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000930 AC: 13AN: 1397922Hom.: 0 Cov.: 30 AF XY: 0.00000870 AC XY: 6AN XY: 689468
GnomAD4 exome
AF:
AC:
13
AN:
1397922
Hom.:
Cov.:
30
AF XY:
AC XY:
6
AN XY:
689468
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152062Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74266
GnomAD4 genome
AF:
AC:
3
AN:
152062
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74266
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Asia WGS
AF:
AC:
2
AN:
3478
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 | Jun 29, 2022 | The c.220G>A (p.V74M) alteration is located in exon 4 (coding exon 4) of the BORCS8 gene. This alteration results from a G to A substitution at nucleotide position 220, causing the valine (V) at amino acid position 74 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
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;D
Vest4
MutPred
Loss of methylation at K75 (P = 0.0249);.;Loss of methylation at K75 (P = 0.0249);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at