Genetic Variant DAGLB:p.Ala656Thr (chr7-6409890-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_139179.4(DAGLB):c.1966G>A(p.Ala656Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,614,122 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 11 hom. )

Consequence

DAGLB
NM_139179.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00400

Variant links:

Genes affected

DAGLB (HGNC:28923): (diacylglycerol lipase beta) Enables lipase activity. Involved in arachidonic acid metabolic process. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

DAGLB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029959679).

BP6

Variant 7-6409890-C-T is Benign according to our data. Variant chr7-6409890-C-T is described in ClinVar as [Benign]. Clinvar id is 768140.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00531 (809/152344) while in subpopulation AFR AF= 0.0187 (779/41570). AF 95% confidence interval is 0.0176. There are 8 homozygotes in gnomad4. There are 403 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAGLB	NM_139179.4 link	c.1966G>A	p.Ala656Thr	missense_variant	Exon 15 of 15	ENST00000297056.11	NP_631918.3	Q8NCG7-1
DAGLB	NM_001142936.2 link	c.1579G>A	p.Ala527Thr	missense_variant	Exon 13 of 13		NP_001136408.1	Q8NCG7-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAGLB	ENST00000297056.11 link	c.1966G>A	p.Ala656Thr	missense_variant	Exon 15 of 15	1	NM_139179.4	ENSP00000297056.6		Q8NCG7-1

Frequencies

GnomAD3 genomes

AF:

0.00531

AC:

809

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00143

AC:

359

AN:

251246

Hom.:

AF XY:

0.00116

AC XY:

158

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.0208

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000581

AC:

850

AN:

1461778

Hom.:

Cov.:

AF XY:

0.000520

AC XY:

378

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.0223

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.00531

AC:

809

AN:

152344

Hom.:

Cov.:

AF XY:

0.00541

AC XY:

403

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0187

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000810

Hom.:

Bravo

AF:

0.00566

ESP6500AA

AF:

0.0163

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00175

AC:

212

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 23, 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

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.8

DANN

Benign

0.42

DEOGEN2

Benign

0.017

T;.;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

L;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

0.67

N;N;N

REVEL

Benign

0.072

Sift

Benign

0.86

T;T;T

Sift4G

Benign

0.59

T;T;T

Polyphen

0.0070

B;.;.

Vest4

0.060

MVP

0.33

MPC

0.049

ClinPred

0.0028

GERP RS

3.9

Varity_R

0.027

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over