rs11893469

Positions:

• chr2-109190687-C-T

Variant summary

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

The NM_001099289.3(SH3RF3):​c.573+60574C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 151,992 control chromosomes in the GnomAD database, including 1,470 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 0.12 (1470 hom., cov: 32)
• Consequence: SH3RF3 NM_001099289.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.901

Genes affected

SH3RF3 (HGNC:24699): (SH3 domain containing ring finger 3) Enables ubiquitin protein ligase activity. Involved in positive regulation of JNK cascade and protein autoubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

RANBP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3RF3	NM_001099289.3	c.573+60574C>T		intron_variant		ENST00000309415.8
SH3RF3	XM_011511109.3	c.573+60574C>T		intron_variant
RANBP2	XM_047445367.1	c.8370+417641C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3RF3	ENST00000309415.8	c.573+60574C>T		intron_variant		5	NM_001099289.3	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18981 AN: 151874 Hom.: 1473 Cov.: 32

Gnomad AFR AF: 0.0532

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0965

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.125 AC: 18973 AN: 151992 Hom.: 1470 Cov.: 32 AF XY: 0.128 AC XY: 9480 AN XY: 74292

Gnomad4 AFR AF: 0.0530

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.0970

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.134

Alfa AF: 0.142 Hom.: 828

Bravo AF: 0.112

Asia WGS AF: 0.117 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.44

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: rs11893469; hg19: chr2-109807143;