chr2-231294499-T-C

Position:

• chr2-231294499-T-C

Variant summary

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

The NM_001352754.2(ARMC9):​c.1718-1699T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,414 control chromosomes in the GnomAD database, including 51,860 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 0.82 (51774 hom., cov: 31)
  • Exomes 𝑓: 0.79 (86 hom.)
• Consequence: ARMC9 NM_001352754.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC9	NM_001352754.2	c.1718-1699T>C		intron_variant		ENST00000611582.5	NP_001339683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC9	ENST00000611582.5	c.1718-1699T>C		intron_variant		5	NM_001352754.2	ENSP00000484804.1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124704 AN: 152024 Hom.: 51715 Cov.: 31

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.801

GnomAD4 exome AF: 0.794 AC: 216 AN: 272 Hom.: 86 Cov.: 0 AF XY: 0.789 AC XY: 161 AN XY: 204

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.917

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.802

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.820 AC: 124816 AN: 152142 Hom.: 51774 Cov.: 31 AF XY: 0.821 AC XY: 61016 AN XY: 74360

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.797

Alfa AF: 0.769 Hom.: 43633

Bravo AF: 0.827

Asia WGS AF: 0.805 AC: 2800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs745962; hg19: chr2-232159212;