chr11-118588354-G-A

Variant names:

• chr11-118588354-G-A
• rs633308
• NM_001655.5:c.819-1987G>A

Variant summary

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

The NM_001655.5(ARCN1):​c.819-1987G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,022 control chromosomes in the GnomAD database, including 36,224 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 0.68 (36224 hom., cov: 31)
• Consequence: ARCN1 NM_001655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 5 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 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.819-1987G>A		intron	N/A	NP_001646.2
	ARCN1	NM_001425073.1		c.819-1987G>A		intron	N/A	NP_001412002.1
	ARCN1	NM_001425074.1		c.816-1987G>A		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.819-1987G>A		intron	N/A	ENSP00000264028.4
	ARCN1	ENST00000359415.8	TSL:1	c.942-1987G>A		intron	N/A	ENSP00000352385.4
	ARCN1	ENST00000392859.7	TSL:2	c.555-1987G>A		intron	N/A	ENSP00000376599.3

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102603 AN: 151904 Hom.: 36165 Cov.: 31

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.676 AC: 102728 AN: 152022 Hom.: 36224 Cov.: 31 AF XY: 0.675 AC XY: 50172 AN XY: 74298

African (AFR) AF: 0.898 AC: 37287 AN: 41506

American (AMR) AF: 0.649 AC: 9896 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2040 AN: 3468

East Asian (EAS) AF: 0.773 AC: 3999 AN: 5176

South Asian (SAS) AF: 0.605 AC: 2911 AN: 4810

European-Finnish (FIN) AF: 0.604 AC: 6369 AN: 10552

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38229 AN: 67952

Other (OTH) AF: 0.637 AC: 1341 AN: 2106

Alfa AF: 0.596 Hom.: 19522

Bravo AF: 0.693

Asia WGS AF: 0.711 AC: 2475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.14
PhyloP100		-1.7
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: rs633308; hg19: chr11-118459069;