rs1315265

Positions:

• chr11-74785835-C-A
• chr11-74785835-C-T

Variant summary

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

The NM_001098638.2(RNF169):​c.503-3791C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,984 control chromosomes in the GnomAD database, including 5,530 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 0.26 (5530 hom., cov: 30)
• Consequence: RNF169 NM_001098638.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

Genes affected

RNF169 (HGNC:26961): (ring finger protein 169) Enables K63-linked polyubiquitin modification-dependent protein binding activity and nucleosome binding activity. Involved in cellular response to DNA damage stimulus and negative regulation of double-strand break repair. Located in cytosol; nuclear lumen; and site of double-strand break. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF169	NM_001098638.2	c.503-3791C>A		intron_variant		ENST00000299563.5	NP_001092108.1
RNF169	XM_011544889.4	c.566-3791C>A		intron_variant			XP_011543191.1
RNF169	XM_047426707.1	c.-164-3791C>A		intron_variant			XP_047282663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF169	ENST00000299563.5	c.503-3791C>A		intron_variant		1	NM_001098638.2	ENSP00000299563	P1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40077 AN: 151866 Hom.: 5524 Cov.: 30

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.264 AC: 40124 AN: 151984 Hom.: 5530 Cov.: 30 AF XY: 0.266 AC XY: 19765 AN XY: 74286

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.282

Alfa AF: 0.232 Hom.: 531

Bravo AF: 0.263

Asia WGS AF: 0.363 AC: 1265 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	1.9
DANN	Benign	0.58

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: rs1315265; hg19: chr11-74496880;