rs309298

Positions:

• chr2-7046319-G-A

Variant summary

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

The NM_001349181.2(RNF144A):​c.747+16104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,166 control chromosomes in the GnomAD database, including 4,776 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 0.22 (4776 hom., cov: 32)
• Consequence: RNF144A NM_001349181.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343

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]

ENSG00000223884 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF144A	NM_001349181.2	c.747+16104G>A		intron_variant			NP_001336110.1
RNF144A	NM_001349185.2	c.747+16104G>A		intron_variant			NP_001336114.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF144A	ENST00000432850.1	c.732+16104G>A		intron_variant		3		ENSP00000411616.1
ENSG00000223884	ENST00000664324.1	n.712-403C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33959 AN: 152048 Hom.: 4767 Cov.: 32

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.223 AC: 33980 AN: 152166 Hom.: 4776 Cov.: 32 AF XY: 0.227 AC XY: 16917 AN XY: 74380

Gnomad4 AFR AF: 0.0560

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.202

Alfa AF: 0.258 Hom.: 967

Bravo AF: 0.220

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs309298; hg19: chr2-7186450;