rs750232469
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_001271938.2(MEGF8):c.3798C>T(p.Arg1266=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000628 in 1,608,914 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 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000056 ( 0 hom. )
Consequence
MEGF8
NM_001271938.2 synonymous
NM_001271938.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.46
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 -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 19-42353811-C-T is Benign according to our data. Variant chr19-42353811-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 540556.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-4.45 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000125 (19/152308) while in subpopulation AMR AF= 0.000588 (9/15300). AF 95% confidence interval is 0.000307. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF8 | NM_001271938.2 | c.3798C>T | p.Arg1266= | synonymous_variant | 22/42 | ENST00000251268.11 | |
MEGF8 | NM_001410.3 | c.3597C>T | p.Arg1199= | synonymous_variant | 21/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF8 | ENST00000251268.11 | c.3798C>T | p.Arg1266= | synonymous_variant | 22/42 | 5 | NM_001271938.2 | A2 | |
MEGF8 | ENST00000334370.8 | c.3597C>T | p.Arg1199= | synonymous_variant | 21/41 | 1 | P2 | ||
MEGF8 | ENST00000378073.5 | c.-3288C>T | 5_prime_UTR_variant | 22/41 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000533 AC: 13AN: 243790Hom.: 0 AF XY: 0.0000680 AC XY: 9AN XY: 132364
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GnomAD4 exome AF: 0.0000563 AC: 82AN: 1456606Hom.: 0 Cov.: 33 AF XY: 0.0000580 AC XY: 42AN XY: 723734
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GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74472
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MEGF8-related Carpenter syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 11, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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