dbSNP rs40357: MBOAT7:c.-434A>G (chr19-54189676-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000431666.6(MBOAT7):c.-434A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 153,324 control chromosomes in the GnomAD database, including 4,030 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4012 hom., cov: 34)

Exomes 𝑓: 0.16 ( 18 hom. )

Consequence

MBOAT7
ENST00000431666.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.28

Publications

6 publications found

Variant links:

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]

MBOAT7 links:

TSEN34 (HGNC:15506): (tRNA splicing endonuclease subunit 34) This gene encodes a catalytic subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from precursor tRNAs. The endonuclease complex is also associated with a pre-mRNA 3-prime end processing factor. A mutation in this gene results in the neurological disorder pontocerebellar hypoplasia type 2. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Oct 2009]

TSEN34 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia type 2C
Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
pontocerebellar hypoplasia type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TSEN34 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (Cadd=1.208).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBOAT7	NM_024298.5 link	c.-342A>G		upstream_gene_variant		ENST00000245615.6	NP_077274.3	Q96N66-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBOAT7	ENST00000245615.6 link	c.-342A>G		upstream_gene_variant		1	NM_024298.5	ENSP00000245615.1		Q96N66-1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33350

AN:

152106

Hom.:

4004

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.233

GnomAD4 exome

AF:

0.155

AC:

171

AN:

1100

Hom.:

Cov.:

AF XY:

0.150

AC XY:

121

AN XY:

808

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.200

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.174

AC:

133

AN:

764

European-Finnish (FIN)

AF:

0.200

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.108

AC:

AN:

286

Other (OTH)

AF:

0.100

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.219

AC:

33380

AN:

152224

Hom.:

4012

Cov.:

AF XY:

0.224

AC XY:

16666

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.191

AC:

7955

AN:

41552

American (AMR)

AF:

0.318

AC:

4867

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

689

AN:

3470

East Asian (EAS)

AF:

0.519

AC:

2685

AN:

5178

South Asian (SAS)

AF:

0.209

AC:

1011

AN:

4832

European-Finnish (FIN)

AF:

0.202

AC:

2145

AN:

10594

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13250

AN:

67984

Other (OTH)

AF:

0.235

AC:

496

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1424

2847

4271

5694

7118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.180

Hom.:

1017

Bravo

AF:

0.228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

CADD

Benign

1.2

(source)

PhyloP100

-1.3

PromoterAI

0.12

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over