rs309276

chr2-7059826-A-G

Variant summary

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

The ENST00000664324.1(ENSG00000223884):n.712-13910T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,122 control chromosomes in the GnomAD database, including 18,849 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 0.49 (18849 hom., cov: 32)
• Consequence: ENST00000664324.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

Genes affected

(HGNC:):

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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF144A	NM_001349181.2	c.748-13336A>G		intron_variant
RNF144A	NM_001349185.2	c.748-8390A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000664324.1	n.712-13910T>C		intron_variant, non_coding_transcript_variant
RNF144A	ENST00000432850.1	c.735-8390A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74096 AN: 152004 Hom.: 18835 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.487 AC: 74142 AN: 152122 Hom.: 18849 Cov.: 32 AF XY: 0.493 AC XY: 36676 AN XY: 74364

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.465

Alfa AF: 0.522 Hom.: 2669

Bravo AF: 0.476

Asia WGS AF: 0.542 AC: 1886 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	0.29
Dann	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs309276; hg19: chr2-7199957;