6-18407512-T-C

Variant summary

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

The NM_182757.4(RNF144B):c.165+7813T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,048 control chromosomes in the GnomAD database, including 31,818 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 0.64 (31818 hom., cov: 32)
• Consequence: RNF144B NM_182757.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

Genes affected

RNF144B (HGNC:21578): (ring finger protein 144B) Enables ubiquitin-protein transferase activity. Involved in negative regulation of apoptotic process and ubiquitin-dependent protein catabolic process. Located in mitochondrial membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF144B	NM_182757.4	c.165+7813T>C		intron_variant		ENST00000259939.4
RNF144B	XM_047418594.1	c.165+7813T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF144B	ENST00000259939.4	c.165+7813T>C		intron_variant		1	NM_182757.4	P1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97893 AN: 151928 Hom.: 31810 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.858

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.644 AC: 97948 AN: 152048 Hom.: 31818 Cov.: 32 AF XY: 0.639 AC XY: 47492 AN XY: 74330

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.669

Alfa AF: 0.682 Hom.: 72411

Bravo AF: 0.644

Asia WGS AF: 0.646 AC: 2244 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.7
Dann	Benign	0.78

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: rs1408263; hg19: chr6-18407743;