Variant 8-30131945-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2

The NM_001100916.2(MBOAT4):c.1306T>C(p.Ter436ArgextTer15) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,542,484 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0084 ( 18 hom., cov: 33)

Exomes 𝑓: 0.00091 ( 17 hom. )

Consequence

MBOAT4
NM_001100916.2 stop_lost

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.53

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 -8 ACMG points.

PM4

Stoplost variant in NM_001100916.2 Downstream stopcodon found after 23 codons.

BP6

Variant 8-30131945-A-G is Benign according to our data. Variant chr8-30131945-A-G is described in ClinVar as [Benign]. Clinvar id is 709877.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00835 (1272/152324) while in subpopulation AFR AF= 0.0292 (1213/41562). AF 95% confidence interval is 0.0278. There are 18 homozygotes in gnomad4. There are 603 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBOAT4	NM_001100916.2 linkuse as main transcript	c.1306T>C	p.Ter436ArgextTer15	stop_lost	3/3	ENST00000320542.4
LEPROTL1	NM_001128208.2 linkuse as main transcript	c.280-5327A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBOAT4	ENST00000320542.4 linkuse as main transcript	c.1306T>C	p.Ter436ArgextTer15	stop_lost	3/3	1	NM_001100916.2	P1	Q96T53-1

Frequencies

GnomAD3 genomes

AF:

0.00833

AC:

1268

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00186

AC:

286

AN:

154122

Hom.:

AF XY:

0.00160

AC XY:

130

AN XY:

81230

show subpopulations

Gnomad AFR exome

AF:

0.0301

Gnomad AMR exome

AF:

0.00141

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000669

Gnomad OTH exome

AF:

0.000690

GnomAD4 exome

AF:

0.000906

AC:

1260

AN:

1390160

Hom.:

Cov.:

AF XY:

0.000795

AC XY:

544

AN XY:

683898

show subpopulations

Gnomad4 AFR exome

AF:

0.0329

Gnomad4 AMR exome

AF:

0.00140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000383

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000392

Gnomad4 OTH exome

AF:

0.00201

GnomAD4 genome

AF:

0.00835

AC:

1272

AN:

152324

Hom.:

Cov.:

AF XY:

0.00810

AC XY:

603

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0292

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.00987

ESP6500AA

AF:

0.0260

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.00260

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.84

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Benign

0.44

MutationTaster

Benign

1.0

D;D;N

Vest4

0.020

GERP RS

3.6

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