8-30132685-C-T

Position:

• chr8-30132685-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.180

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 -14 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_single_submitter, 1 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	UniProt
MBOAT4	NM_001100916.2	c.566G>A	p.Arg189His	missense_variant	3/3	ENST00000320542.4
LEPROTL1	NM_001128208.2	c.280-4587C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBOAT4	ENST00000320542.4	c.566G>A	p.Arg189His	missense_variant	3/3	1	NM_001100916.2	P1
LEPROTL1	ENST00000442880.6	c.394+196C>T		intron_variant		2
LEPROTL1	ENST00000523116.5	c.280-4587C>T		intron_variant		2
LEPROTL1	ENST00000520739.5	c.279+28199C>T		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00661 AC: 1005 AN: 152150 Hom.: 11 Cov.: 32

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.: 3 AF XY: 0.00100 AC XY: 83 AN XY: 82898

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.: 15 Cov.: 34 AF XY: 0.000627 AC XY: 433 AN XY: 690238

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.: 11 Cov.: 32 AF XY: 0.00674 AC XY: 502 AN XY: 74464

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.: 0

Bravo AF: 0.00720

ESP6500AA AF: 0.0260 AC: 36

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00233 AC: 61

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.62
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.075
Sift	Benign	0.56	T
Sift4G	Benign	0.61	T
Polyphen		0.0030	B
Vest4		0.056
MVP		0.45
ClinPred		0.0042	T
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

Other links and lift over

dbSNP: rs61745343; hg19: chr8-29990201;