chr7-6409853-C-T

Variant names:

• chr7-6409853-C-T
• rs375537082
• NM_139179.4:c.2003G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_139179.4(DAGLB):​c.2003G>A​(p.Ser668Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DAGLB NM_139179.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.661
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031969726).
• BP6: Variant 7-6409853-C-T is Benign according to our data. Variant chr7-6409853-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3080023.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2003G>A	p.Ser668Asn	missense	Exon 15 of 15	NP_631918.3	Q8NCG7-1
	DAGLB	NM_001142936.2		c.1616G>A	p.Ser539Asn	missense	Exon 13 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.2003G>A	p.Ser668Asn	missense	Exon 15 of 15	ENSP00000297056.6	Q8NCG7-1
	DAGLB	ENST00000878465.1		c.2111G>A	p.Ser704Asn	missense	Exon 16 of 16	ENSP00000548524.1
	DAGLB	ENST00000878464.1		c.1997G>A	p.Ser666Asn	missense	Exon 15 of 15	ENSP00000548523.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461626 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727124

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0070
DANN	Benign	0.16
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.99	N
PhyloP100		-0.66
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.069
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.024
MutPred		0.22		Loss of disorder (P = 0.0338)
MVP		0.18
MPC		0.047
ClinPred		0.039	T
GERP RS		-12
Varity_R		0.044
gMVP		0.17
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: rs375537082; hg19: chr7-6449484; COSMIC: COSV105116559; COSMIC: COSV105116559;