rs17122278

Variant names:

• chr11-118578655-A-G
• rs17122278
• NM_001655.5:c.4-2591A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001655.5(ARCN1):​c.4-2591A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,092 control chromosomes in the GnomAD database, including 1,806 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1806 hom., cov: 31)
• Consequence: ARCN1 NM_001655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394
• Publications: 14 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARCN1	NM_001655.5	MANE Select	c.4-2591A>G		intron	N/A	NP_001646.2
	ARCN1	NM_001425073.1		c.4-2591A>G		intron	N/A	NP_001412002.1
	ARCN1	NM_001425074.1		c.4-2591A>G		intron	N/A	NP_001412003.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARCN1	ENST00000264028.5	TSL:1 MANE Select	c.4-2591A>G		intron	N/A	ENSP00000264028.4
	ARCN1	ENST00000359415.8	TSL:1	c.127-2591A>G		intron	N/A	ENSP00000352385.4
	ARCN1	ENST00000392859.7	TSL:2	c.4-4524A>G		intron	N/A	ENSP00000376599.3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17662 AN: 151974 Hom.: 1809 Cov.: 31

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0752

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.117

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.116 AC: 17653 AN: 152092 Hom.: 1806 Cov.: 31 AF XY: 0.122 AC XY: 9068 AN XY: 74348

African (AFR) AF: 0.0260 AC: 1081 AN: 41516

American (AMR) AF: 0.0749 AC: 1143 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3470

East Asian (EAS) AF: 0.514 AC: 2654 AN: 5162

South Asian (SAS) AF: 0.331 AC: 1594 AN: 4820

European-Finnish (FIN) AF: 0.161 AC: 1700 AN: 10556

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8570 AN: 67998

Other (OTH) AF: 0.125 AC: 263 AN: 2112

Alfa AF: 0.101 Hom.: 223

Bravo AF: 0.103

Asia WGS AF: 0.413 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.9
DANN	Benign	0.41
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs17122278; hg19: chr11-118449370;