rs7231421

Variant names:

• chr18-46368580-C-T
• rs7231421
• NM_152470.3:c.61+34245C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ARK2C	NM_152470.3	c.61+34245C>T		intron_variant	Intron 1 of 7	ENST00000269439.12	NP_689683.2
ARK2C	NM_001256758.1	c.-92+34245C>T		intron_variant	Intron 1 of 5		NP_001243687.1
ARK2C	XM_011526016.4	c.61+34245C>T		intron_variant	Intron 1 of 6		XP_011524318.1
ARK2C	XM_017025788.3	c.61+34245C>T		intron_variant	Intron 1 of 3		XP_016881277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARK2C	ENST00000269439.12	c.61+34245C>T		intron_variant	Intron 1 of 7	2	NM_152470.3	ENSP00000269439.6
ARK2C	ENST00000593230.5	c.-141+41633C>T		intron_variant	Intron 1 of 4	3		ENSP00000467730.1
ARK2C	ENST00000543885.2	c.-92+34245C>T		intron_variant	Intron 1 of 5	2		ENSP00000444285.1
ARK2C	ENST00000586604.5	n.61+34245C>T		intron_variant	Intron 1 of 5	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

African (AFR) AF: 0.275 AC: 11412 AN: 41516

American (AMR) AF: 0.0591 AC: 904 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3470

East Asian (EAS) AF: 0.0935 AC: 484 AN: 5174

South Asian (SAS) AF: 0.0350 AC: 169 AN: 4830

European-Finnish (FIN) AF: 0.0855 AC: 907 AN: 10614

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0364 AC: 2479 AN: 68018

Other (OTH) AF: 0.0818 AC: 173 AN: 2114

Alfa AF: 0.0568 Hom.: 976

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
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7231421; hg19: chr18-43948543;