Genetic Variant ARGLU1:p.Ter274Ter (chr13-106543996-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_018011.4(ARGLU1):c.822A>G(p.Ter274Ter) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000922 in 1,582,790 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 1 hom. )

Consequence

ARGLU1
NM_018011.4 stop_retained

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.25

Publications

0 publications found

Variant links:

Genes affected

ARGLU1 (HGNC:25482): (arginine and glutamate rich 1) Enables cadherin binding activity. Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ARGLU1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 13-106543996-T-C is Benign according to our data. Variant chr13-106543996-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3034677.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=3.25 with no splicing effect.

BS2

High AC in GnomAd4 at 55 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018011.4. 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
	ARGLU1	NM_018011.4	MANE Select	c.822A>G	p.Ter274Ter	stop_retained	Exon 4 of 4	NP_060481.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARGLU1	ENST00000400198.8	TSL:1 MANE Select	c.822A>G	p.Ter274Ter	stop_retained	Exon 4 of 4	ENSP00000383059.3	Q9NWB6-1
ARGLU1	ENST00000952389.1		c.915A>G	p.Ter305Ter	stop_retained	Exon 5 of 5	ENSP00000622448.1
ARGLU1	ENST00000868085.1		c.819A>G	p.Ter273Ter	stop_retained	Exon 4 of 4	ENSP00000538144.1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000879

AC:

AN:

216204

AF XY:

0.0000679

show subpopulations

Gnomad AFR exome

AF:

0.000730

Gnomad AMR exome

AF:

0.0000751

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000594

Gnomad OTH exome

AF:

0.000191

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1430570

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

710496

show subpopulations

African (AFR)

AF:

0.000679

AC:

AN:

30948

American (AMR)

AF:

0.0000540

AC:

AN:

37052

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25380

East Asian (EAS)

AF:

0.00

AC:

AN:

38232

South Asian (SAS)

AF:

0.0000127

AC:

AN:

78584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53122

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.0000517

AC:

AN:

1102574

Other (OTH)

AF:

0.000152

AC:

AN:

59110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.000361

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00118

AC:

AN:

41552

American (AMR)

AF:

0.0000654

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000235

Hom.:

Bravo

AF:

0.000355

Asia WGS

AF:

0.000578

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ARGLU1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over