rs420013

Positions:

• chr2-7021455-C-A
• chr2-7021455-C-G
• chr2-7021455-C-T

Variant summary

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

The NM_014746.6(RNF144A):​c.509+775C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,732 control chromosomes in the GnomAD database, including 16,390 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 0.45 (16390 hom., cov: 31)
• Consequence: RNF144A NM_014746.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

Genes affected

RNF144A (HGNC:20457): (ring finger protein 144A) This gene encodes a member of a family of RING finger domain-containing E3 ubiquitin ligases that also includes parkin and parc. The expression of this gene is induced by DNA damage. The encoded protein interacts with the cytoplasmic DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) and promotes its degradation through ubiquitination. The orthologous mouse protein has been shown to interact with a ubiquitin-conjugating enzyme involved in embryonic development. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF144A	NM_014746.6	c.509+775C>A		intron_variant		ENST00000320892.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF144A	ENST00000320892.11	c.509+775C>A		intron_variant		1	NM_014746.6	P1
RNF144A	ENST00000432850.1	c.496+775C>A		intron_variant		3
RNF144A	ENST00000467276.5	n.630+687C>A		intron_variant, non_coding_transcript_variant		3
RNF144A	ENST00000480970.1	n.555+775C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68196 AN: 151614 Hom.: 16361 Cov.: 31

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.450 AC: 68269 AN: 151732 Hom.: 16390 Cov.: 31 AF XY: 0.458 AC XY: 33957 AN XY: 74154

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.444

Alfa AF: 0.470 Hom.: 7651

Bravo AF: 0.443

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.082
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs420013; hg19: chr2-7161586;