rs309276

Variant names:

• chr2-7059826-A-G
• rs309276
• NM_001349181.2:c.748-13336A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349181.2(RNF144A):​c.748-13336A>G variant causes a intron 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: RNF144A NM_001349181.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RNF144A	NM_001349181.2	c.748-13336A>G		intron_variant	Intron 8 of 9		NP_001336110.1
RNF144A	NM_001349185.2	c.748-8390A>G		intron_variant	Intron 8 of 9		NP_001336114.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF144A	ENST00000432850.1	c.733-8390A>G		intron_variant	Intron 6 of 6	3		ENSP00000411616.1
ENSG00000223884	ENST00000415520.6	n.720-1491T>C		intron_variant	Intron 4 of 4	4
ENSG00000223884	ENST00000664324.2	n.712-13910T>C		intron_variant	Intron 2 of 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

African (AFR) AF: 0.340 AC: 14124 AN: 41486

American (AMR) AF: 0.545 AC: 8340 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2006 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1906 AN: 5178

South Asian (SAS) AF: 0.677 AC: 3263 AN: 4820

European-Finnish (FIN) AF: 0.587 AC: 6212 AN: 10576

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36820 AN: 67976

Other (OTH) AF: 0.465 AC: 983 AN: 2114

Alfa AF: 0.516 Hom.: 2723

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
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs309276; hg19: chr2-7199957;