chr19-4543675-C-A
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_032108.4(SEMA6B):c.2593G>T(p.Ala865Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 1,230,714 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
SEMA6B
NM_032108.4 missense
NM_032108.4 missense
Scores
1
1
13
Clinical Significance
Conservation
PhyloP100: -0.0580
Genes affected
SEMA6B (HGNC:10739): (semaphorin 6B) This gene encodes a member of the semaphorin family, a group of proteins characterized by the presence of a conserved semaphorin (sema) domain. Whereas some semaphorins are transmembrane proteins, others are secreted. Semaphorins play a major role in axon guidance. The protein encoded by this gene may be involved in both peripheral and central nervous system development. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0014801323).
BP6
Variant 19-4543675-C-A is Benign according to our data. Variant chr19-4543675-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2355486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0011 (168/152274) while in subpopulation AFR AF= 0.00385 (160/41570). AF 95% confidence interval is 0.00336. There are 0 homozygotes in gnomad4. There are 77 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 168 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMA6B | NM_032108.4 | c.2593G>T | p.Ala865Ser | missense_variant | 17/17 | ENST00000586582.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA6B | ENST00000586582.6 | c.2593G>T | p.Ala865Ser | missense_variant | 17/17 | 1 | NM_032108.4 | P1 | |
SEMA6B | ENST00000586965.1 | c.1852-579G>T | intron_variant | 1 | |||||
SEMA6B | ENST00000676793.1 | c.2593G>T | p.Ala865Ser | missense_variant | 17/17 | P1 | |||
SEMA6B | ENST00000677828.1 | c.*1855G>T | 3_prime_UTR_variant, NMD_transcript_variant | 17/17 |
Frequencies
GnomAD3 genomes AF: 0.00106 AC: 162AN: 152166Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
162
AN:
152166
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: 0.00169 AC: 1AN: 590Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 342
GnomAD3 exomes
AF:
AC:
1
AN:
590
Hom.:
AF XY:
AC XY:
0
AN XY:
342
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: 0.000110 AC: 119AN: 1078440Hom.: 0 Cov.: 32 AF XY: 0.000110 AC XY: 56AN XY: 509222
GnomAD4 exome
AF:
AC:
119
AN:
1078440
Hom.:
Cov.:
32
AF XY:
AC XY:
56
AN XY:
509222
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: 0.00110 AC: 168AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.00103 AC XY: 77AN XY: 74448
GnomAD4 genome
AF:
AC:
168
AN:
152274
Hom.:
Cov.:
32
AF XY:
AC XY:
77
AN XY:
74448
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
SEMA6B-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 09, 2022 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N;N;N
PrimateAI
Pathogenic
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of glycosylation at A865 (P = 0.029);
MVP
MPC
ClinPred
T
GERP RS
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