11-74785835-C-A

Variant names:

• chr11-74785835-C-A
• rs1315265
• NM_001098638.2:c.503-3791C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RNF169	NM_001098638.2	c.503-3791C>A		intron_variant	Intron 1 of 5	ENST00000299563.5	NP_001092108.1
RNF169	XM_011544889.4	c.566-3791C>A		intron_variant	Intron 1 of 5		XP_011543191.1
RNF169	XM_047426707.1	c.-164-3791C>A		intron_variant	Intron 1 of 5		XP_047282663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF169	ENST00000299563.5	c.503-3791C>A		intron_variant	Intron 1 of 5	1	NM_001098638.2	ENSP00000299563.4

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

African (AFR) AF: 0.322 AC: 13346 AN: 41420

American (AMR) AF: 0.244 AC: 3724 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1233 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1395 AN: 5180

South Asian (SAS) AF: 0.417 AC: 2009 AN: 4822

European-Finnish (FIN) AF: 0.223 AC: 2346 AN: 10538

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15117 AN: 67964

Other (OTH) AF: 0.282 AC: 594 AN: 2110

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
PhyloP100		-0.20
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: rs1315265; hg19: chr11-74496880;