NM_139179.4:c.1787T>C

Variant names:

• chr7-6410163-A-G
• rs139753251
• NM_139179.4:c.1787T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_139179.4(DAGLB):​c.1787T>C​(p.Ile596Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00805 in 1,580,808 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (78 hom.)
• Consequence: DAGLB NM_139179.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.11
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011635125).
• BP6: Variant 7-6410163-A-G is Benign according to our data. Variant chr7-6410163-A-G is described in ClinVar as Benign. ClinVar VariationId is 771156.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139179.4. 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
	DAGLB	NM_139179.4	MANE Select	c.1787T>C	p.Ile596Thr	missense	Exon 14 of 15	NP_631918.3	Q8NCG7-1
	DAGLB	NM_001142936.2		c.1400T>C	p.Ile467Thr	missense	Exon 12 of 13	NP_001136408.1	Q8NCG7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAGLB	ENST00000297056.11	TSL:1 MANE Select	c.1787T>C	p.Ile596Thr	missense	Exon 14 of 15	ENSP00000297056.6	Q8NCG7-1
	DAGLB	ENST00000878465.1		c.1895T>C	p.Ile632Thr	missense	Exon 15 of 16	ENSP00000548524.1
	DAGLB	ENST00000878464.1		c.1781T>C	p.Ile594Thr	missense	Exon 14 of 15	ENSP00000548523.1

Frequencies

GnomAD3 genomes AF: 0.00703 AC: 1069 AN: 152074 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00703 AC: 1508 AN: 214474 AF XY: 0.00698

Gnomad AFR exome AF: 0.00126

Gnomad AMR exome AF: 0.00364

Gnomad ASJ exome AF: 0.00546

Gnomad EAS exome AF: 0.0000595

Gnomad FIN exome AF: 0.0180

Gnomad NFE exome AF: 0.00946

Gnomad OTH exome AF: 0.00863

GnomAD4 exome AF: 0.00816 AC: 11663 AN: 1428616 Hom.: 78 Cov.: 32 AF XY: 0.00815 AC XY: 5757 AN XY: 706472

African (AFR) AF: 0.00125 AC: 41 AN: 32912

American (AMR) AF: 0.00416 AC: 170 AN: 40882

Ashkenazi Jewish (ASJ) AF: 0.00465 AC: 113 AN: 24316

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38980

South Asian (SAS) AF: 0.00198 AC: 163 AN: 82464

European-Finnish (FIN) AF: 0.0166 AC: 864 AN: 52024

Middle Eastern (MID) AF: 0.00177 AC: 10 AN: 5636

European-Non Finnish (NFE) AF: 0.00901 AC: 9839 AN: 1092478

Other (OTH) AF: 0.00784 AC: 462 AN: 58924

GnomAD4 genome AF: 0.00702 AC: 1069 AN: 152192 Hom.: 9 Cov.: 32 AF XY: 0.00696 AC XY: 518 AN XY: 74406

African (AFR) AF: 0.00164 AC: 68 AN: 41534

American (AMR) AF: 0.00563 AC: 86 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4824

European-Finnish (FIN) AF: 0.0156 AC: 165 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0105 AC: 714 AN: 68006

Other (OTH) AF: 0.00711 AC: 15 AN: 2110

Alfa AF: 0.00969 Hom.: 9

Bravo AF: 0.00553

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.000909 AC: 4

ESP6500EA AF: 0.00803 AC: 69

ExAC AF: 0.00631 AC: 765

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.012	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.86
MVP		0.80
MPC		0.25
ClinPred		0.018	T
GERP RS		5.9
Varity_R		0.42
gMVP		0.90
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139753251; hg19: chr7-6449794; COSMIC: COSV99032299; COSMIC: COSV99032299;