11-118581258-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001655.5(ARCN1):c.16G>T(p.Ala6Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000922 in 1,614,188 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00091 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 10 hom. )

Consequence

ARCN1
NM_001655.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 9.52

Publications

5 publications found

Variant links:

Genes affected

ARCN1 (HGNC:649): (archain 1) This gene maps in a region, which include the mixed lineage leukemia and Friend leukemia virus integration 1 genes, where multiple disease-associated chromosome translocations occur. It is an intracellular protein. Archain sequences are well conserved among eukaryotes and this protein may play a fundamental role in eukaryotic cell biology. It has similarities to heat shock proteins and clathrin-associated proteins, and may be involved in vesicle structure or trafficking. [provided by RefSeq, Jul 2008]

ARCN1 Gene-Disease associations (from GenCC):

short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay
Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ARCN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011251539).

BP6

Variant 11-118581258-G-T is Benign according to our data. Variant chr11-118581258-G-T is described in ClinVar as Benign. ClinVar VariationId is 718665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 139 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001655.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ARCN1	NM_001655.5	MANE Select	c.16G>T	p.Ala6Ser	missense	Exon 2 of 10	NP_001646.2
ARCN1	NM_001425073.1		c.16G>T	p.Ala6Ser	missense	Exon 2 of 11	NP_001412002.1
ARCN1	NM_001425074.1		c.16G>T	p.Ala6Ser	missense	Exon 2 of 10	NP_001412003.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARCN1	ENST00000264028.5	TSL:1 MANE Select	c.16G>T	p.Ala6Ser	missense	Exon 2 of 10	ENSP00000264028.4	P48444-1
ARCN1	ENST00000359415.8	TSL:1	c.139G>T	p.Ala47Ser	missense	Exon 3 of 11	ENSP00000352385.4	B0YIW6
ARCN1	ENST00000935081.1		c.16G>T	p.Ala6Ser	missense	Exon 2 of 11	ENSP00000605140.1

Frequencies

GnomAD3 genomes

AF:

0.000913

AC:

139

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0121

Gnomad SAS

AF:

0.00725

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00208

AC:

523

AN:

251460

AF XY:

0.00223

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.0113

Gnomad FIN exome

AF:

0.00180

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000923

AC:

1349

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

797

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00122

AC:

AN:

26134

East Asian (EAS)

AF:

0.0118

AC:

470

AN:

39698

South Asian (SAS)

AF:

0.00668

AC:

576

AN:

86258

European-Finnish (FIN)

AF:

0.00144

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000746

AC:

AN:

1111958

Other (OTH)

AF:

0.00177

AC:

107

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

176

265

353

441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.000912

AC:

139

AN:

152352

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41594

American (AMR)

AF:

0.000719

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.0121

AC:

AN:

5188

South Asian (SAS)

AF:

0.00725

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68038

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000717

Hom.:

Bravo

AF:

0.000650

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00215

AC:

261

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

ARCN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.32

MutationAssessor

Benign

2.0

PhyloP100

9.5

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.43

Sift

Benign

0.035

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.70

MVP

0.65

MPC

1.4

ClinPred

0.063

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.37

gMVP

0.77

Mutation Taster

=17/83

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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