rs7115634

Variant names:

• chr11-118595534-A-G
• rs7115634
• NM_001655.5:c.1241+1836A>G

Variant summary

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

The ENST00000264028.5(ARCN1):​c.1241+1836A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,234 control chromosomes in the GnomAD database, including 2,132 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 0.14 (2132 hom., cov: 32)
• Consequence: ARCN1 ENST00000264028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.12
• Publications: 8 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000264028.5. 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.1241+1836A>G		intron	N/A	NP_001646.2
	ARCN1	NM_001425073.1		c.1304+1468A>G		intron	N/A	NP_001412002.1
	ARCN1	NM_001425074.1		c.1238+1836A>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.1241+1836A>G		intron	N/A	ENSP00000264028.4
	ARCN1	ENST00000359415.8	TSL:1	c.1364+1836A>G		intron	N/A	ENSP00000352385.4
	ARCN1	ENST00000392859.7	TSL:2	c.977+1836A>G		intron	N/A	ENSP00000376599.3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21694 AN: 152116 Hom.: 2136 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.143 AC: 21701 AN: 152234 Hom.: 2132 Cov.: 32 AF XY: 0.147 AC XY: 10941 AN XY: 74442

African (AFR) AF: 0.116 AC: 4818 AN: 41530

American (AMR) AF: 0.0872 AC: 1334 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3470

East Asian (EAS) AF: 0.515 AC: 2666 AN: 5172

South Asian (SAS) AF: 0.333 AC: 1604 AN: 4822

European-Finnish (FIN) AF: 0.162 AC: 1713 AN: 10604

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

European-Non Finnish (NFE) AF: 0.127 AC: 8611 AN: 68018

Other (OTH) AF: 0.144 AC: 305 AN: 2116

Alfa AF: 0.125 Hom.: 246

Bravo AF: 0.133

Asia WGS AF: 0.422 AC: 1467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0060
DANN	Benign	0.61
PhyloP100		-4.1
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: rs7115634; hg19: chr11-118466249;