8-30132685-C-T

Position:

chr8-30132685-C-T

Variant summary

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

The NM_001100916.2(MBOAT4):c.566G>A(p.Arg189His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,551,722 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 15 hom. )

Consequence

MBOAT4
NM_001100916.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.180

Variant links:

Genes affected

MBOAT4 (HGNC:32311): (membrane bound O-acyltransferase domain containing 4) Enables serine O-acyltransferase activity. Involved in peptidyl-serine octanoylation. Predicted to be located in endoplasmic reticulum. Predicted to be active in membrane. Predicted to be integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

MBOAT4 links:

LEPROTL1 (HGNC:6555): (leptin receptor overlapping transcript like 1) Enables identical protein binding activity. Predicted to be involved in late endosome to vacuole transport via multivesicular body sorting pathway and negative regulation of growth hormone receptor signaling pathway. Predicted to be integral component of membrane. Predicted to be active in endosome. [provided by Alliance of Genome Resources, Apr 2022]

LEPROTL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010284573).

BP6

Variant 8-30132685-C-T is Benign according to our data. Variant chr8-30132685-C-T is described in ClinVar as [Benign]. Clinvar id is 734148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0066 (1005/152268) while in subpopulation AFR AF= 0.0228 (948/41540). AF 95% confidence interval is 0.0216. There are 11 homozygotes in gnomad4. There are 502 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBOAT4	NM_001100916.2 link	c.566G>A	p.Arg189His	missense_variant	3/3	ENST00000320542.4	NP_001094386.1	Q96T53-1
LEPROTL1	NM_001128208.2 link	c.280-4587C>T		intron_variant			NP_001121680.1	O95214-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MBOAT4	ENST00000320542.4 link	c.566G>A	p.Arg189His	missense_variant	3/3	1	NM_001100916.2	ENSP00000314196.3	Q96T53-1
LEPROTL1	ENST00000523116.5 link	c.280-4587C>T		intron_variant		2		ENSP00000428281.1	O95214-2
LEPROTL1	ENST00000442880.6 link	c.394+196C>T		intron_variant		2		ENSP00000412803.2	C9JVM4
LEPROTL1	ENST00000520739.5 link	n.279+28199C>T		intron_variant		4		ENSP00000429398.1	E5RIL0

Frequencies

GnomAD3 genomes

AF:

0.00661

AC:

1005

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00148

AC:

231

AN:

156464

Hom.:

AF XY:

0.00100

AC XY:

AN XY:

82898

show subpopulations

Gnomad AFR exome

AF:

0.0225

Gnomad AMR exome

AF:

0.000891

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.000184

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000594

Gnomad NFE exome

AF:

0.000314

Gnomad OTH exome

AF:

0.00159

GnomAD4 exome

AF:

0.000707

AC:

989

AN:

1399454

Hom.:

Cov.:

AF XY:

0.000627

AC XY:

433

AN XY:

690238

show subpopulations

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.000168

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00660

AC:

1005

AN:

152268

Hom.:

Cov.:

AF XY:

0.00674

AC XY:

502

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.000853

Hom.:

Bravo

AF:

0.00720

ESP6500AA

AF:

0.0260

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00233

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.033

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.56

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.22

PROVEAN

Benign

1.4

REVEL

Benign

0.075

Sift

Benign

0.56

Sift4G

Benign

0.61

Polyphen

0.0030

Vest4

0.056

MVP

0.45

ClinPred

0.0042

GERP RS

1.8

Varity_R

0.057

gMVP

0.14

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