rs10736492

Variant names:

• chr11-118588554-A-G
• rs10736492
• NM_001655.5:c.819-1787A>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.819-1787A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,096 control chromosomes in the GnomAD database, including 14,250 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 0.43 (14250 hom., cov: 33)
• Consequence: ARCN1 NM_001655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARCN1	NM_001655.5	c.819-1787A>G		intron_variant	Intron 5 of 9	ENST00000264028.5	NP_001646.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARCN1	ENST00000264028.5	c.819-1787A>G		intron_variant	Intron 5 of 9	1	NM_001655.5	ENSP00000264028.4
ARCN1	ENST00000359415.8	c.942-1787A>G		intron_variant	Intron 6 of 10	1		ENSP00000352385.4
ARCN1	ENST00000392859.7	c.555-1787A>G		intron_variant	Intron 4 of 8	2		ENSP00000376599.3
ARCN1	ENST00000534182.2	c.159+7153A>G		intron_variant	Intron 2 of 2	5		ENSP00000431676.1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65226 AN: 151974 Hom.: 14233 Cov.: 33

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.429 AC: 65283 AN: 152096 Hom.: 14250 Cov.: 33 AF XY: 0.428 AC XY: 31818 AN XY: 74370

African (AFR) AF: 0.429 AC: 17798 AN: 41510

American (AMR) AF: 0.510 AC: 7790 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3472

East Asian (EAS) AF: 0.246 AC: 1269 AN: 5168

South Asian (SAS) AF: 0.265 AC: 1280 AN: 4822

European-Finnish (FIN) AF: 0.440 AC: 4657 AN: 10582

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29558 AN: 67968

Other (OTH) AF: 0.427 AC: 901 AN: 2112

Alfa AF: 0.440 Hom.: 45357

Bravo AF: 0.440

Asia WGS AF: 0.260 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.38
PhyloP100		0.34
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: rs10736492; hg19: chr11-118459269;