rs1868929

Variant names:

• chr2-231318878-C-T
• rs1868929
• NM_001352754.2:c.1774-12915C>T

Variant summary

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

The NM_001352754.2(ARMC9):​c.1774-12915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,152 control chromosomes in the GnomAD database, including 8,942 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 0.24 (8942 hom., cov: 32)
• Consequence: ARMC9 NM_001352754.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 4 publications found

Genes affected

ARMC9 (HGNC:20730): (armadillo repeat containing 9) Predicted to be involved in cilium assembly and positive regulation of smoothened signaling pathway. Located in centriole and ciliary basal body. Implicated in Joubert syndrome 30. [provided by Alliance of Genome Resources, Apr 2022]

ARMC9 Gene-Disease associations (from GenCC):

• Joubert syndrome 30

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC9	NM_001352754.2	c.1774-12915C>T		intron_variant	Intron 19 of 24	ENST00000611582.5	NP_001339683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC9	ENST00000611582.5	c.1774-12915C>T		intron_variant	Intron 19 of 24	5	NM_001352754.2	ENSP00000484804.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36651 AN: 152034 Hom.: 8905 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.0470

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.242 AC: 36749 AN: 152152 Hom.: 8942 Cov.: 32 AF XY: 0.243 AC XY: 18107 AN XY: 74394

African (AFR) AF: 0.597 AC: 24743 AN: 41458

American (AMR) AF: 0.204 AC: 3118 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0790 AC: 274 AN: 3470

East Asian (EAS) AF: 0.552 AC: 2851 AN: 5166

South Asian (SAS) AF: 0.288 AC: 1390 AN: 4830

European-Finnish (FIN) AF: 0.0592 AC: 628 AN: 10600

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.0470 AC: 3197 AN: 68008

Other (OTH) AF: 0.209 AC: 441 AN: 2114

Alfa AF: 0.126 Hom.: 11124

Bravo AF: 0.267

Asia WGS AF: 0.448 AC: 1557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.020
DANN	Benign	0.71
PhyloP100		-1.9
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: rs1868929; hg19: chr2-232183591;