chr2-7063197-A-G

Variant names:

• chr2-7063197-A-G
• rs6746899
• NM_001349181.2:c.748-9965A>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.748-9965A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,218 control chromosomes in the GnomAD database, including 1,445 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 0.14 (1445 hom., cov: 32)
• Consequence: RNF144A NM_001349181.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF144A	NM_001349181.2	c.748-9965A>G		intron_variant	Intron 8 of 9		NP_001336110.1
RNF144A	NM_001349185.2	c.748-5019A>G		intron_variant	Intron 8 of 9		NP_001336114.1
LOC101929452	NR_110252.1	n.343-283T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF144A	ENST00000432850.1	c.733-5019A>G		intron_variant	Intron 6 of 6	3		ENSP00000411616.1
ENSG00000223884	ENST00000415520.6	n.343-283T>C		intron_variant	Intron 2 of 4	4
ENSG00000223884	ENST00000649356.2	n.1010-283T>C		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20551 AN: 152100 Hom.: 1442 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0666

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.135 AC: 20564 AN: 152218 Hom.: 1445 Cov.: 32 AF XY: 0.138 AC XY: 10255 AN XY: 74424

African (AFR) AF: 0.156 AC: 6469 AN: 41524

American (AMR) AF: 0.104 AC: 1594 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 619 AN: 3472

East Asian (EAS) AF: 0.0669 AC: 346 AN: 5172

South Asian (SAS) AF: 0.122 AC: 588 AN: 4828

European-Finnish (FIN) AF: 0.219 AC: 2314 AN: 10590

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8306 AN: 68018

Other (OTH) AF: 0.126 AC: 267 AN: 2112

Alfa AF: 0.126 Hom.: 705

Bravo AF: 0.127

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.71
PhyloP100		0.32

Splicing

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

Other links and lift over

dbSNP: rs6746899; hg19: chr2-7203328;