5-159176563-T-C

Variant names:

• chr5-159176563-T-C
• rs1473247
• NM_001199383.2:c.621+69A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001199383.2(RNF145):​c.621+69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 927,510 control chromosomes in the GnomAD database, including 54,818 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 0.41 (15057 hom., cov: 32)
  • Exomes 𝑓: 0.30 (39761 hom.)
• Consequence: RNF145 NM_001199383.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 21 publications found

Genes affected

RNF145 (HGNC:20853): (ring finger protein 145) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF145	NM_001199383.2	c.621+69A>G		intron_variant	Intron 5 of 10	ENST00000424310.7	NP_001186312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF145	ENST00000424310.7	c.621+69A>G		intron_variant	Intron 5 of 10	1	NM_001199383.2	ENSP00000409064.2

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61676 AN: 151814 Hom.: 15030 Cov.: 32

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.304 AC: 235873 AN: 775578 Hom.: 39761 AF XY: 0.308 AC XY: 123358 AN XY: 400754

African (AFR) AF: 0.680 AC: 12686 AN: 18650

American (AMR) AF: 0.489 AC: 12973 AN: 26506

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 5988 AN: 17286

East Asian (EAS) AF: 0.423 AC: 14963 AN: 35360

South Asian (SAS) AF: 0.448 AC: 25156 AN: 56172

European-Finnish (FIN) AF: 0.250 AC: 12251 AN: 48964

Middle Eastern (MID) AF: 0.385 AC: 1612 AN: 4182

European-Non Finnish (NFE) AF: 0.260 AC: 138076 AN: 531740

Other (OTH) AF: 0.331 AC: 12168 AN: 36718

GnomAD4 genome AF: 0.406 AC: 61757 AN: 151932 Hom.: 15057 Cov.: 32 AF XY: 0.408 AC XY: 30276 AN XY: 74258

African (AFR) AF: 0.672 AC: 27842 AN: 41458

American (AMR) AF: 0.449 AC: 6848 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1138 AN: 3462

East Asian (EAS) AF: 0.366 AC: 1893 AN: 5174

South Asian (SAS) AF: 0.444 AC: 2137 AN: 4816

European-Finnish (FIN) AF: 0.256 AC: 2702 AN: 10560

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17858 AN: 67906

Other (OTH) AF: 0.425 AC: 897 AN: 2112

Alfa AF: 0.319 Hom.: 27865

Bravo AF: 0.432

Asia WGS AF: 0.472 AC: 1641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.38
PhyloP100		-0.11
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: rs1473247; hg19: chr5-158603571; COSMIC: COSV50876319; COSMIC: COSV50876319;