rs117439608
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_001271938.2(MEGF8):c.402C>T(p.Asn134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000944 in 1,613,840 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00077 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00096 ( 16 hom. )
Consequence
MEGF8
NM_001271938.2 synonymous
NM_001271938.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.761
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 19-42334057-C-T is Benign according to our data. Variant chr19-42334057-C-T is described in ClinVar as [Benign]. Clinvar id is 540551.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.761 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000768 (117/152312) while in subpopulation EAS AF= 0.0195 (101/5176). AF 95% confidence interval is 0.0164. There are 2 homozygotes in gnomad4. There are 63 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF8 | NM_001271938.2 | c.402C>T | p.Asn134= | synonymous_variant | 3/42 | ENST00000251268.11 | |
MEGF8 | NM_001410.3 | c.402C>T | p.Asn134= | synonymous_variant | 3/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF8 | ENST00000251268.11 | c.402C>T | p.Asn134= | synonymous_variant | 3/42 | 5 | NM_001271938.2 | A2 | |
MEGF8 | ENST00000334370.8 | c.402C>T | p.Asn134= | synonymous_variant | 3/41 | 1 | P2 | ||
MEGF8 | ENST00000378073.5 | c.-6684C>T | 5_prime_UTR_variant | 3/41 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000769 AC: 117AN: 152194Hom.: 2 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
117
AN:
152194
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: 0.00115 AC: 287AN: 248614Hom.: 2 AF XY: 0.000948 AC XY: 128AN XY: 134952
GnomAD3 exomes
AF:
AC:
287
AN:
248614
Hom.:
AF XY:
AC XY:
128
AN XY:
134952
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: 0.000963 AC: 1407AN: 1461528Hom.: 16 Cov.: 31 AF XY: 0.000912 AC XY: 663AN XY: 727050
GnomAD4 exome
AF:
AC:
1407
AN:
1461528
Hom.:
Cov.:
31
AF XY:
AC XY:
663
AN XY:
727050
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: 0.000768 AC: 117AN: 152312Hom.: 2 Cov.: 32 AF XY: 0.000846 AC XY: 63AN XY: 74468
GnomAD4 genome
?
AF:
AC:
117
AN:
152312
Hom.:
Cov.:
32
AF XY:
AC XY:
63
AN XY:
74468
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:
Asia WGS
AF:
AC:
29
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MEGF8-related Carpenter syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 06, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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