12-56214143-C-T

Position:

• chr12-56214143-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000345093.9(RNF41):​c.-23-73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 815,010 control chromosomes in the GnomAD database, including 341,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (51885 hom., cov: 31)
  • Exomes 𝑓: 0.93 (289603 hom.)
• Consequence: RNF41 ENST00000345093.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.296

Genes affected

RNF41 (HGNC:18401): (ring finger protein 41) This gene encodes an E3 ubiquitin ligase. The encoded protein plays a role in type 1 cytokine receptor signaling by controlling the balance between JAK2-associated cytokine receptor degradation and ectodomain shedding. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2011]

RNF41 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-56214143-C-T is Benign according to our data. Variant chr12-56214143-C-T is described in ClinVar as [Benign]. Clinvar id is 1234461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF41	NM_005785.4	c.-23-73G>A		intron_variant		ENST00000345093.9	NP_005776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF41	ENST00000345093.9	c.-23-73G>A		intron_variant		1	NM_005785.4	ENSP00000342755.4

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119495 AN: 152046 Hom.: 51890 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.850

GnomAD4 exome AF: 0.930 AC: 616244 AN: 662846 Hom.: 289603 AF XY: 0.934 AC XY: 333806 AN XY: 357452

Gnomad4 AFR exome AF: 0.371

Gnomad4 AMR exome AF: 0.939

Gnomad4 ASJ exome AF: 0.910

Gnomad4 EAS exome AF: 0.982

Gnomad4 SAS exome AF: 0.955

Gnomad4 FIN exome AF: 0.946

Gnomad4 NFE exome AF: 0.947

Gnomad4 OTH exome AF: 0.899

GnomAD4 genome AF: 0.785 AC: 119510 AN: 152164 Hom.: 51885 Cov.: 31 AF XY: 0.791 AC XY: 58856 AN XY: 74398

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.897

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.979

Gnomad4 SAS AF: 0.958

Gnomad4 FIN AF: 0.947

Gnomad4 NFE AF: 0.948

Gnomad4 OTH AF: 0.847

Alfa AF: 0.915 Hom.: 64274

Bravo AF: 0.763

Asia WGS AF: 0.909 AC: 3161 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.4
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4759218; hg19: chr12-56607927;