Variant 19-42360759-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001271938.2(MEGF8):c.5489-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,560,654 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0071 ( 5 hom., cov: 32)

Exomes 𝑓: 0.010 ( 120 hom. )

Consequence

MEGF8
NM_001271938.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0370

Variant links:

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]

MEGF8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-42360759-C-T is Benign according to our data. Variant chr19-42360759-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00712 (1085/152356) while in subpopulation NFE AF= 0.0128 (873/68026). AF 95% confidence interval is 0.0121. There are 5 homozygotes in gnomad4. There are 479 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEGF8	NM_001271938.2 linkuse as main transcript	c.5489-16C>T		intron_variant		ENST00000251268.11	NP_001258867.1	Q7Z7M0-1
MEGF8	NM_001410.3 linkuse as main transcript	c.5288-16C>T		intron_variant			NP_001401.2	Q7Z7M0-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MEGF8	ENST00000251268.11 linkuse as main transcript	c.5489-16C>T	intron_variant	5	NM_001271938.2	ENSP00000251268.5	Q7Z7M0-1
MEGF8	ENST00000334370.8 linkuse as main transcript	c.5288-16C>T	intron_variant	1		ENSP00000334219.4	Q7Z7M0-2
MEGF8	ENST00000378073.5 linkuse as main transcript	c.-1597-16C>T	intron_variant	5		ENSP00000367313.4	F5GZG7

Frequencies

GnomAD3 genomes

AF:

0.00713

AC:

1085

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00588

AC:

977

AN:

166170

Hom.:

AF XY:

0.00562

AC XY:

499

AN XY:

88858

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.00296

Gnomad ASJ exome

AF:

0.00174

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000547

Gnomad FIN exome

AF:

0.00327

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.00541

GnomAD4 exome

AF:

0.0105

AC:

14718

AN:

1408298

Hom.:

120

Cov.:

AF XY:

0.0102

AC XY:

7069

AN XY:

695616

show subpopulations

Gnomad4 AFR exome

AF:

0.00181

Gnomad4 AMR exome

AF:

0.00266

Gnomad4 ASJ exome

AF:

0.00210

Gnomad4 EAS exome

AF:

0.0000547

Gnomad4 SAS exome

AF:

0.000549

Gnomad4 FIN exome

AF:

0.00335

Gnomad4 NFE exome

AF:

0.0128

Gnomad4 OTH exome

AF:

0.00771

GnomAD4 genome

AF:

0.00712

AC:

1085

AN:

152356

Hom.:

Cov.:

AF XY:

0.00643

AC XY:

479

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00228

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00407

Hom.:

Bravo

AF:

0.00677

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 19, 2017	- -

MEGF8-related Carpenter syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.61

DANN

Benign

0.46

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over