rs7231421

Positions:

• chr18-46368580-C-T

Variant summary

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

The NM_152470.3(ARK2C):​c.61+34245C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,240 control chromosomes in the GnomAD database, including 1,770 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 0.11 (1770 hom., cov: 33)
• Consequence: ARK2C NM_152470.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

Genes affected

ARK2C (HGNC:31696): (arkadia (RNF111) C-terminal like ring finger ubiquitin ligase 2C) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in motor neuron axon guidance and positive regulation of BMP signaling pathway. Predicted to act upstream of or within several processes, including forelimb morphogenesis; multicellular organism aging; and nervous system development. Predicted to be part of protein-containing complex. Predicted to be active in nucleus. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARK2C	NM_152470.3	c.61+34245C>T		intron_variant		ENST00000269439.12	NP_689683.2
ARK2C	NM_001256758.1	c.-92+34245C>T		intron_variant			NP_001243687.1
ARK2C	XM_011526016.4	c.61+34245C>T		intron_variant			XP_011524318.1
ARK2C	XM_017025788.3	c.61+34245C>T		intron_variant			XP_016881277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF165	ENST00000269439.12	c.61+34245C>T		intron_variant		2	NM_152470.3	ENSP00000269439.6
RNF165	ENST00000593230.5	c.-141+41633C>T		intron_variant		3		ENSP00000467730.1
RNF165	ENST00000543885.2	c.-92+34245C>T		intron_variant		2		ENSP00000444285.1
RNF165	ENST00000586604.5	n.61+34245C>T		intron_variant		2		ENSP00000468365.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16623 AN: 152122 Hom.: 1762 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0935

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0855

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0832

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

GnomAD4 genome AF: 0.109 AC: 16656 AN: 152240 Hom.: 1770 Cov.: 33 AF XY: 0.109 AC XY: 8103 AN XY: 74440

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.0591

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.0935

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0855

Gnomad4 NFE AF: 0.0364

Gnomad4 OTH AF: 0.0818

Alfa AF: 0.0492 Hom.: 566

Bravo AF: 0.117

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7231421; hg19: chr18-43948543;