chr8-30132393-G-A

Variant names:

• chr8-30132393-G-A
• rs16876562
• NM_001100916.2:c.858C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001100916.2(MBOAT4):​c.858C>T​(p.Pro286Pro) 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MBOAT4	NM_001100916.2	c.858C>T	p.Pro286Pro	synonymous_variant	Exon 3 of 3	ENST00000320542.4	NP_001094386.1
LEPROTL1	NM_001128208.2	c.280-4879G>A		intron_variant	Intron 3 of 3		NP_001121680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBOAT4	ENST00000320542.4	c.858C>T	p.Pro286Pro	synonymous_variant	Exon 3 of 3	1	NM_001100916.2	ENSP00000314196.3

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

GnomAD2 exomes AF: 0.00582 AC: 909 AN: 156300 AF XY: 0.00465

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 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 AC: 3075 AN: 31598

Gnomad4 AMR exome AF: 0.00507 AC: 181 AN: 35706

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25182

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35738

Gnomad4 SAS exome AF: 0.000328 AC: 26 AN: 79232

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 49278

Gnomad4 NFE exome AF: 0.0000695 AC: 75 AN: 1078976

Gnomad4 Remaining exome AF: 0.00565 AC: 328 AN: 58002

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 AC: 0.0929242 AN: 0.0929242

Gnomad4 AMR AF: 0.00949 AC: 0.00948705 AN: 0.00948705

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000415 AC: 0.000414594 AN: 0.000414594

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000221 AC: 0.000220543 AN: 0.000220543

Gnomad4 OTH AF: 0.0223 AC: 0.0222749 AN: 0.0222749

Alfa AF: 0.0130 Hom.: 57

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
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
Mutation Taster		=99/1	polymorphism (auto)

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;