6-148440226-C-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_015278.5(SASH1):āc.328C>Gā(p.Gln110Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00134 in 1,614,052 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.0071 ( 18 hom., cov: 31)
Exomes š: 0.00074 ( 10 hom. )
Consequence
SASH1
NM_015278.5 missense
NM_015278.5 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 5.43
Genes affected
SASH1 (HGNC:19182): (SAM and SH3 domain containing 1) This gene encodes a scaffold protein involved in the TLR4 signaling pathway that may stimulate cytokine production and endothelial cell migration in response to invading pathogens. The encoded protein has also been described as a potential tumor suppressor that may negatively regulate proliferation, apoptosis, and invasion of cancer cells, and reduced expression of this gene has been observed in multiple human cancers. Mutations in this gene may be associated with abnormal skin pigmentation in human patients. [provided by RefSeq, Oct 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.008813471).
BP6
Variant 6-148440226-C-G is Benign according to our data. Variant chr6-148440226-C-G is described in ClinVar as [Benign]. Clinvar id is 716141.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00706 (1074/152194) while in subpopulation AFR AF= 0.0245 (1019/41532). AF 95% confidence interval is 0.0233. There are 18 homozygotes in gnomad4. There are 536 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 18 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SASH1 | NM_015278.5 | c.328C>G | p.Gln110Glu | missense_variant | 3/20 | ENST00000367467.8 | NP_056093.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SASH1 | ENST00000367467.8 | c.328C>G | p.Gln110Glu | missense_variant | 3/20 | 1 | NM_015278.5 | ENSP00000356437 | P1 | |
SASH1 | ENST00000367469.5 | n.246C>G | non_coding_transcript_exon_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00708 AC: 1076AN: 152076Hom.: 18 Cov.: 31
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GnomAD3 exomes AF: 0.00183 AC: 461AN: 251432Hom.: 10 AF XY: 0.00132 AC XY: 179AN XY: 135892
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GnomAD4 exome AF: 0.000742 AC: 1085AN: 1461858Hom.: 10 Cov.: 31 AF XY: 0.000667 AC XY: 485AN XY: 727226
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GnomAD4 genome AF: 0.00706 AC: 1074AN: 152194Hom.: 18 Cov.: 31 AF XY: 0.00721 AC XY: 536AN XY: 74392
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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