Variant rs141582110 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001271938.2(MEGF8):c.2299-15_2299-12delTCAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 1,604,856 control chromosomes in the GnomAD database, including 46 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 44 hom. )

Consequence

MEGF8
NM_001271938.2 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.349

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 -16 ACMG points.

BP6

Variant 19-42349479-ATCAC-A is Benign according to our data. Variant chr19-42349479-ATCAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 446027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00317 (482/152060) while in subpopulation SAS AF= 0.0145 (70/4820). AF 95% confidence interval is 0.0118. There are 2 homozygotes in gnomad4. There are 258 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	Protein	UniProt
MEGF8	NM_001271938.2 linkuse as main transcript	c.2299-15_2299-12delTCAC		intron_variant		ENST00000251268.11	NP_001258867.1	Q7Z7M0-1
MEGF8	NM_001410.3 linkuse as main transcript	c.2098-15_2098-12delTCAC		intron_variant			NP_001401.2	Q7Z7M0-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MEGF8	ENST00000251268.11 linkuse as main transcript	c.2299-15_2299-12delTCAC	intron_variant	5	NM_001271938.2	ENSP00000251268.5	Q7Z7M0-1
MEGF8	ENST00000334370.8 linkuse as main transcript	c.2098-15_2098-12delTCAC	intron_variant	1		ENSP00000334219.4	Q7Z7M0-2
MEGF8	ENST00000378073.5 linkuse as main transcript	c.-4787-15_-4787-12delTCAC	intron_variant	5		ENSP00000367313.4	F5GZG7

Frequencies

GnomAD3 genomes

AF:

0.00318

AC:

483

AN:

151944

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000629

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.00688

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00406

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00538

AC:

1296

AN:

240788

Hom.:

AF XY:

0.00591

AC XY:

772

AN XY:

130726

show subpopulations

Gnomad AFR exome

AF:

0.000515

Gnomad AMR exome

AF:

0.00115

Gnomad ASJ exome

AF:

0.00114

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.0135

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.00547

Gnomad OTH exome

AF:

0.00696

GnomAD4 exome

AF:

0.00485

AC:

7050

AN:

1452796

Hom.:

AF XY:

0.00522

AC XY:

3766

AN XY:

721830

show subpopulations

Gnomad4 AFR exome

AF:

0.000661

Gnomad4 AMR exome

AF:

0.00115

Gnomad4 ASJ exome

AF:

0.000971

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0139

Gnomad4 FIN exome

AF:

0.0107

Gnomad4 NFE exome

AF:

0.00438

Gnomad4 OTH exome

AF:

0.00553

GnomAD4 genome

AF:

0.00317

AC:

482

AN:

152060

Hom.:

Cov.:

AF XY:

0.00347

AC XY:

258

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.000627

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.0145

Gnomad4 FIN

AF:

0.00688

Gnomad4 NFE

AF:

0.00406

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00364

Hom.:

Bravo

AF:

0.00229

Asia WGS

AF:

0.00606

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 29, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 28, 2017	- -

MEGF8-related Carpenter syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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