8-30132393-G-A

Position:

• chr8-30132393-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001100916.2(MBOAT4):​c.858C>T​(p.Pro286=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00501 in 1,551,660 control chromosomes in the GnomAD database, including 358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (202 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (156 hom.)
• Consequence: MBOAT4 NM_001100916.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.62

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]

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017038882).
• BP6: Variant 8-30132393-G-A is Benign according to our data. Variant chr8-30132393-G-A is described in ClinVar as [Benign]. Clinvar id is 784126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.62 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBOAT4	NM_001100916.2	c.858C>T	p.Pro286=	synonymous_variant	3/3	ENST00000320542.4
LEPROTL1	NM_001128208.2	c.280-4879G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBOAT4	ENST00000320542.4	c.858C>T	p.Pro286=	synonymous_variant	3/3	1	NM_001100916.2	P1
LEPROTL1	ENST00000442880.6	c.298G>A	p.Gly100Arg	missense_variant	4/5	2
LEPROTL1	ENST00000523116.5	c.280-4879G>A		intron_variant		2
LEPROTL1	ENST00000520739.5	c.279+27907G>A		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4047 AN: 152132 Hom.: 199 Cov.: 32

Gnomad AFR AF: 0.0926

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00950

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.00582 AC: 909 AN: 156300 Hom.: 42 AF XY: 0.00465 AC XY: 385 AN XY: 82840

Gnomad AFR exome AF: 0.0986

Gnomad AMR exome AF: 0.00421

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000307

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000829

Gnomad OTH exome AF: 0.00274

GnomAD4 exome AF: 0.00265 AC: 3702 AN: 1399410 Hom.: 156 Cov.: 34 AF XY: 0.00227 AC XY: 1567 AN XY: 690214

Gnomad4 AFR exome AF: 0.0973

Gnomad4 AMR exome AF: 0.00507

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000328

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000695

Gnomad4 OTH exome AF: 0.00565

GnomAD4 genome AF: 0.0267 AC: 4072 AN: 152250 Hom.: 202 Cov.: 32 AF XY: 0.0258 AC XY: 1921 AN XY: 74440

Gnomad4 AFR AF: 0.0929

Gnomad4 AMR AF: 0.00949

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0124 Hom.: 44

Bravo AF: 0.0308

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0816 AC: 113

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00868 AC: 217

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.90	T
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.072
DANN	Benign	0.34
DEOGEN2	Benign	0.092	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.58	T
MutationTaster	Benign	1.0	D;N;D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.041
Sift	Benign	0.14	T
Sift4G	Benign	0.37	T
Vest4		0.22
MutPred		0.85		Gain of MoRF binding (P = 0.0217);
MVP		0.068
ClinPred		0.0099	T
GERP RS		-10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs16876562; hg19: chr8-29989909; COSMIC: COSV104628867; COSMIC: COSV104628867;