rs7580717

Positions:

• chr2-231311828-G-A
• chr2-231311828-G-C
• chr2-231311828-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352754.2(ARMC9):​c.1773+15575G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 146,396 control chromosomes in the GnomAD database, including 6,740 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 0.30 (6740 hom., cov: 28)
• Consequence: ARMC9 NM_001352754.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC9	NM_001352754.2	c.1773+15575G>A		intron_variant		ENST00000611582.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC9	ENST00000611582.5	c.1773+15575G>A		intron_variant		5	NM_001352754.2	P1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 43342 AN: 146332 Hom.: 6740 Cov.: 28

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.0904

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.296 AC: 43351 AN: 146396 Hom.: 6740 Cov.: 28 AF XY: 0.292 AC XY: 20702 AN XY: 70922

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.0912

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.300

Alfa AF: 0.312 Hom.: 7881

Bravo AF: 0.278

Asia WGS AF: 0.138 AC: 481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.74

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: rs7580717; hg19: chr2-232176541;