rs79199039

chr19-54174099-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024298.5(MBOAT7):c.1364G>A(p.Arg455Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,607,288 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R455W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0086 (13 hom., cov: 32)
  • Exomes 𝑓: 0.011 (101 hom.)
• Consequence: MBOAT7 NM_024298.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0690

Genes affected

MBOAT7 (HGNC:15505): (membrane bound O-acyltransferase domain containing 7) This gene encodes a member of the membrane-bound O-acyltransferases family of integral membrane proteins that have acyltransferase activity. The encoded protein is a lysophosphatidylinositol acyltransferase that has specificity for arachidonoyl-CoA as an acyl donor. This protein is involved in the reacylation of phospholipids as part of the phospholipid remodeling pathway known as the Land cycle. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027557313).
• BP6: Variant 19-54174099-C-T is Benign according to our data. Variant chr19-54174099-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-54174099-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00856 (1303/152152) while in subpopulation NFE AF= 0.0133 (907/67988). AF 95% confidence interval is 0.0126. There are 13 homozygotes in gnomad4. There are 590 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBOAT7	NM_024298.5	c.1364G>A	p.Arg455Gln	missense_variant	8/8	ENST00000245615.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBOAT7	ENST00000245615.6	c.1364G>A	p.Arg455Gln	missense_variant	8/8	1	NM_024298.5	P1

Frequencies

GnomAD3 genomes AF: 0.00854 AC: 1299 AN: 152032 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00857 AC: 2077 AN: 242364 Hom.: 15 AF XY: 0.00892 AC XY: 1176 AN XY: 131806

Gnomad AFR exome AF: 0.00199

Gnomad AMR exome AF: 0.00215

Gnomad ASJ exome AF: 0.0178

Gnomad EAS exome AF: 0.000113

Gnomad SAS exome AF: 0.00303

Gnomad FIN exome AF: 0.0104

Gnomad NFE exome AF: 0.0132

Gnomad OTH exome AF: 0.0101

GnomAD4 exome AF: 0.0109 AC: 15862 AN: 1455136 Hom.: 101 Cov.: 31 AF XY: 0.0107 AC XY: 7728 AN XY: 723862

Gnomad4 AFR exome AF: 0.00133

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.0185

Gnomad4 EAS exome AF: 0.0000761

Gnomad4 SAS exome AF: 0.00337

Gnomad4 FIN exome AF: 0.0123

Gnomad4 NFE exome AF: 0.0123

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.00856 AC: 1303 AN: 152152 Hom.: 13 Cov.: 32 AF XY: 0.00793 AC XY: 590 AN XY: 74418

Gnomad4 AFR AF: 0.00229

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.0105 Hom.: 9

Bravo AF: 0.00703

TwinsUK AF: 0.00836 AC: 31

ALSPAC AF: 0.0101 AC: 39

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.0138 AC: 119

ExAC AF: 0.00960 AC: 1165

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign/Likely 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	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	MBOAT7: BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 10, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	16
Dann	Uncertain	1.0
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.16	N
MetaRNN	Benign	0.0028	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.94	N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.029
Sift	Benign	0.061	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.028	B;B;B
Vest4		0.10
MVP		0.28
MPC		0.20
ClinPred		0.010	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071
gMVP		0.31

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: rs79199039; hg19: chr19-54677793; COSMIC: COSV99825176; COSMIC: COSV99825176;