rs145886667
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001271938.2(MEGF8):c.7041C>T(p.Asp2347=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,588,454 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0017 ( 0 hom., cov: 27)
Exomes 𝑓: 0.0021 ( 8 hom. )
Consequence
MEGF8
NM_001271938.2 synonymous
NM_001271938.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.75
Genes affected
MEGF8 (HGNC:3233): (multiple EGF like domains 8) The protein encoded by this gene is a single-pass type I membrane protein of unknown function that contains several EGF-like domains, Kelch repeats, and PSI domains. Defects in this gene are a cause of Carpenter syndrome 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 19-42370736-C-T is Benign according to our data. Variant chr19-42370736-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 473341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.75 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00172 (260/151206) while in subpopulation NFE AF= 0.00167 (113/67780). AF 95% confidence interval is 0.00142. There are 0 homozygotes in gnomad4. There are 147 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF8 | NM_001271938.2 | c.7041C>T | p.Asp2347= | synonymous_variant | 40/42 | ENST00000251268.11 | |
MEGF8 | NM_001410.3 | c.6840C>T | p.Asp2280= | synonymous_variant | 39/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF8 | ENST00000251268.11 | c.7041C>T | p.Asp2347= | synonymous_variant | 40/42 | 5 | NM_001271938.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00172 AC: 260AN: 151088Hom.: 0 Cov.: 27
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GnomAD3 exomes AF: 0.00219 AC: 465AN: 212192Hom.: 1 AF XY: 0.00236 AC XY: 268AN XY: 113550
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GnomAD4 exome AF: 0.00213 AC: 3068AN: 1437248Hom.: 8 Cov.: 32 AF XY: 0.00217 AC XY: 1549AN XY: 712422
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GnomAD4 genome ? AF: 0.00172 AC: 260AN: 151206Hom.: 0 Cov.: 27 AF XY: 0.00199 AC XY: 147AN XY: 73790
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
MEGF8-related Carpenter syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 21, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | MEGF8: BP4, BP7 - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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