rs1463003111

Variant names:

• chr7-6410317-T-C
• rs1463003111
• NM_139179.4:c.1633A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-6410317-T-C
• chr7-6410317-T-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139179.4(DAGLB):​c.1633A>G​(p.Thr545Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T545K) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: DAGLB NM_139179.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.88
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2571965).

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.1633A>G	p.Thr545Ala	missense	Exon 14 of 15	NP_631918.3	Q8NCG7-1
	DAGLB	NM_001142936.2		c.1246A>G	p.Thr416Ala	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.1633A>G	p.Thr545Ala	missense	Exon 14 of 15	ENSP00000297056.6	Q8NCG7-1
	DAGLB	ENST00000878465.1		c.1741A>G	p.Thr581Ala	missense	Exon 15 of 16	ENSP00000548524.1
	DAGLB	ENST00000878464.1		c.1627A>G	p.Thr543Ala	missense	Exon 14 of 15	ENSP00000548523.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251036 AF XY: 0.00

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74332

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.059	T
Eigen	Benign	0.097
Eigen_PC	Benign	0.0060
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.9
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.20
Sift	Benign	0.15	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.60
MutPred		0.28		Loss of glycosylation at T545 (P = 0.0314)
MVP		0.50
MPC		0.14
ClinPred		0.44	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.64
Mutation Taster		=54/46	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: rs1463003111; hg19: chr7-6449948;