rs6741819

Positions:

• chr2-7007842-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.136-6612C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,062 control chromosomes in the GnomAD database, including 7,553 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 0.31 (7553 hom., cov: 33)
• Consequence: RNF144A NM_014746.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF144A	NM_014746.6	c.136-6612C>T		intron_variant		ENST00000320892.11	NP_055561.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF144A	ENST00000320892.11	c.136-6612C>T		intron_variant		1	NM_014746.6	ENSP00000321330	P1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46687 AN: 151944 Hom.: 7553 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.0674

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.307 AC: 46699 AN: 152062 Hom.: 7553 Cov.: 33 AF XY: 0.306 AC XY: 22765 AN XY: 74320

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.0676

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.306

Alfa AF: 0.280 Hom.: 7577

Bravo AF: 0.307

Asia WGS AF: 0.120 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.57

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: rs6741819; hg19: chr2-7147973;