rs6746899

Positions:

• chr2-7063197-A-G

Variant summary

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

The NR_110252.1(LOC101929452):​n.343-283T>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 0.135 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: LOC101929452 NR_110252.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323

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=-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/exons	MANE	Protein	UniProt
LOC101929452	NR_110252.1	n.343-283T>C		intron_variant, non_coding_transcript_variant
RNF144A	NM_001349181.2	c.748-9965A>G		intron_variant			NP_001336110.1
RNF144A	NM_001349185.2	c.748-5019A>G		intron_variant			NP_001336114.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000664324.1	n.711+13685T>C		intron_variant, non_coding_transcript_variant
RNF144A	ENST00000432850.1	c.735-5019A>G		intron_variant		3		ENSP00000411616
	ENST00000415520.5	n.343-283T>C		intron_variant, non_coding_transcript_variant		4
	ENST00000649356.2	n.1010-283T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.0669

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.126

Alfa AF: 0.127 Hom.: 650

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6746899; hg19: chr2-7203328;