8-30132685-C-T

Variant names:

• chr8-30132685-C-T
• rs61745343
• NM_001100916.2:c.566G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R189C) has been classified as Likely 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.180
• Publications: 4 publications found

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 -20 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 VariationId is 734148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100916.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBOAT4	NM_001100916.2	MANE Select	c.566G>A	p.Arg189His	missense	Exon 3 of 3	NP_001094386.1	Q96T53-1
	LEPROTL1	NM_001128208.2		c.280-4587C>T		intron	N/A	NP_001121680.1	O95214-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBOAT4	ENST00000320542.4	TSL:1 MANE Select	c.566G>A	p.Arg189His	missense	Exon 3 of 3	ENSP00000314196.3	Q96T53-1
	LEPROTL1	ENST00000523116.5	TSL:2	c.280-4587C>T		intron	N/A	ENSP00000428281.1	O95214-2
	LEPROTL1	ENST00000442880.6	TSL:2	c.394+196C>T		intron	N/A	ENSP00000412803.2	C9JVM4

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

GnomAD2 exomes AF: 0.00148 AC: 231 AN: 156464 AF XY: 0.00100

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 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

African (AFR) AF: 0.0224 AC: 707 AN: 31598

American (AMR) AF: 0.00106 AC: 38 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25182

East Asian (EAS) AF: 0.000168 AC: 6 AN: 35738

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79236

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49308

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5698

European-Non Finnish (NFE) AF: 0.000147 AC: 159 AN: 1078976

Other (OTH) AF: 0.00126 AC: 73 AN: 58014

GnomAD4 genome AF: 0.00660 AC: 1005 AN: 152268 Hom.: 11 Cov.: 32 AF XY: 0.00674 AC XY: 502 AN XY: 74464

African (AFR) AF: 0.0228 AC: 948 AN: 41540

American (AMR) AF: 0.00177 AC: 27 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68026

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00243 Hom.: 6

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.18
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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs61745343; hg19: chr8-29990201;