2-6953961-A-C

Variant names:

• chr2-6953961-A-C
• rs771314
• NM_014746.6:c.-12+12814A>C

Variant summary

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

The NM_014746.6(RNF144A):​c.-12+12814A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,088 control chromosomes in the GnomAD database, including 61,129 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 0.89 (61129 hom., cov: 32)
• Consequence: RNF144A NM_014746.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF144A	NM_014746.6	c.-12+12814A>C		intron_variant	Intron 2 of 8	ENST00000320892.11	NP_055561.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF144A	ENST00000320892.11	c.-12+12814A>C		intron_variant	Intron 2 of 8	1	NM_014746.6	ENSP00000321330.6
RNF144A	ENST00000416587.5	c.-12+12814A>C		intron_variant	Intron 2 of 3	5		ENSP00000414420.1
RNF144A	ENST00000467276.5	n.334+12814A>C		intron_variant	Intron 2 of 5	3
RNF144A	ENST00000480970.1	n.347+12814A>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135923 AN: 151970 Hom.: 61067 Cov.: 32

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.893

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

GnomAD4 genome AF: 0.894 AC: 136042 AN: 152088 Hom.: 61129 Cov.: 32 AF XY: 0.889 AC XY: 66114 AN XY: 74338

African (AFR) AF: 0.976 AC: 40529 AN: 41524

American (AMR) AF: 0.851 AC: 13023 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3072 AN: 3468

East Asian (EAS) AF: 0.740 AC: 3827 AN: 5172

South Asian (SAS) AF: 0.828 AC: 3993 AN: 4820

European-Finnish (FIN) AF: 0.848 AC: 8906 AN: 10506

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.879 AC: 59755 AN: 67988

Other (OTH) AF: 0.891 AC: 1879 AN: 2108

Alfa AF: 0.858 Hom.: 2725

Bravo AF: 0.895

Asia WGS AF: 0.826 AC: 2859 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.57
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs771314; hg19: chr2-7094092;