Genetic Variant ARCN1:c.3+8C>T (chr11-118572558-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001655.5(ARCN1):c.3+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000905 in 1,609,086 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00093 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 9 hom. )

Consequence

ARCN1
NM_001655.5 splice_region, intron

Scores

Splicing: ADA: 0.0001177

Clinical Significance

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

Conservation

PhyloP100: -1.16

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 links:

IFT46 (HGNC:26146): (intraflagellar transport 46) Predicted to enable protein C-terminus binding activity. Predicted to be involved in cilium assembly; intraciliary transport; and protein stabilization. Predicted to act upstream of or within smoothened signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IFT46 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 11-118572558-C-T is Benign according to our data. Variant chr11-118572558-C-T is described in ClinVar as [Benign]. Clinvar id is 718664.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 142 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARCN1	NM_001655.5 link	c.3+8C>T		splice_region_variant, intron_variant	Intron 1 of 9	ENST00000264028.5	NP_001646.2	P48444-1B0YIW5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARCN1	ENST00000264028.5 link	c.3+8C>T		splice_region_variant, intron_variant	Intron 1 of 9	1	NM_001655.5	ENSP00000264028.4		P48444-1

Frequencies

GnomAD3 genomes

AF:

0.000933

AC:

142

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0121

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00210

AC:

486

AN:

231866

Hom.:

AF XY:

0.00222

AC XY:

282

AN XY:

126814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000596

Gnomad ASJ exome

AF:

0.00135

Gnomad EAS exome

AF:

0.0108

Gnomad SAS exome

AF:

0.00755

Gnomad FIN exome

AF:

0.00181

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00106

GnomAD4 exome

AF:

0.000902

AC:

1314

AN:

1456764

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

775

AN XY:

724354

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00123

Gnomad4 EAS exome

AF:

0.0116

Gnomad4 SAS exome

AF:

0.00656

Gnomad4 FIN exome

AF:

0.00140

Gnomad4 NFE exome

AF:

0.0000721

Gnomad4 OTH exome

AF:

0.00178

GnomAD4 genome

AF:

0.000932

AC:

142

AN:

152322

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0122

Gnomad4 SAS

AF:

0.00725

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000274

Hom.:

Bravo

AF:

0.000657

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ARCN1: BP4, BS1, BS2 -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ARCN1-related disorder

Benign:1

Aug 13, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.5

DANN

Benign

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over