rs17122278

Positions:

• chr11-118578655-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARCN1	NM_001655.5	c.4-2591A>G		intron_variant		ENST00000264028.5
ARCN1	NM_001142281.2	c.4-4524A>G		intron_variant
ARCN1	XM_005271542.5	c.4-2591A>G		intron_variant
ARCN1	XM_047426899.1	c.4-4524A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARCN1	ENST00000264028.5	c.4-2591A>G		intron_variant		1	NM_001655.5	P1
ARCN1	ENST00000359415.8	c.127-2591A>G		intron_variant		1
ARCN1	ENST00000392859.7	c.4-4524A>G		intron_variant		2
ARCN1	ENST00000534182.2	c.4-2591A>G		intron_variant		5

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

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.0749

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.125

Alfa AF: 0.103 Hom.: 223

Bravo AF: 0.103

Asia WGS AF: 0.413 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.9
DANN	Benign	0.41

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

LitVar

Other links and lift over

dbSNP: rs17122278; hg19: chr11-118449370;