2-231327593-C-T

Variant names:

• chr2-231327593-C-T
• rs1669070
• NM_001352754.2:c.1774-4200C>T

Variant summary

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

The NM_001352754.2(ARMC9):​c.1774-4200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,010 control chromosomes in the GnomAD database, including 9,972 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 0.36 (9972 hom., cov: 32)
• Consequence: ARMC9 NM_001352754.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC9	NM_001352754.2	c.1774-4200C>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.1774-4200C>T		intron_variant	Intron 19 of 24	5	NM_001352754.2	ENSP00000484804.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54010 AN: 151892 Hom.: 9964 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.356 AC: 54053 AN: 152010 Hom.: 9972 Cov.: 32 AF XY: 0.361 AC XY: 26824 AN XY: 74310

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.375

Alfa AF: 0.370 Hom.: 8982

Bravo AF: 0.345

Asia WGS AF: 0.357 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.33

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: rs1669070; hg19: chr2-232192305;