rs4799327

chr18-32095029-G-A

Variant summary

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

The NM_016271.5(RNF138):c.110+2143G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,120 control chromosomes in the GnomAD database, including 2,219 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 0.17 (2219 hom., cov: 33)
• Consequence: RNF138 NM_016271.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

Genes affected

RNF138 (HGNC:17765): (ring finger protein 138) The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF138	NM_016271.5	c.110+2143G>A		intron_variant		ENST00000261593.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF138	ENST00000261593.8	c.110+2143G>A		intron_variant		1	NM_016271.5	P1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25402 AN: 152002 Hom.: 2211 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0955

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.167 AC: 25447 AN: 152120 Hom.: 2219 Cov.: 33 AF XY: 0.170 AC XY: 12654 AN XY: 74380

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0959

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.175

Alfa AF: 0.156 Hom.: 4048

Bravo AF: 0.164

Asia WGS AF: 0.169 AC: 590 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	3.3
Dann	Benign	0.57

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: rs4799327; hg19: chr18-29674992;