9-36419532-A-G

Position:

• chr9-36419532-A-G

Variant summary

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

The XM_047422794.1(RNF38):​c.324+5081T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,132 control chromosomes in the GnomAD database, including 41,794 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 0.74 (41794 hom., cov: 33)
• Consequence: RNF38 XM_047422794.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

RNF38 (HGNC:18052): (ring finger protein 38) This gene encodes a protein with a coiled-coil motif and a RING-H2 motif (C3H2C2) at its carboxy-terminus. The RING motif is a zinc-binding domain found in a large set of proteins playing roles in diverse cellular processes including oncogenesis, development, signal transduction, and apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF38	XM_011517712.3	c.-238+5081T>C		intron_variant
RNF38	XM_017014294.2	c.143+5081T>C		intron_variant
RNF38	XM_017014296.2	c.17+5081T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF38	ENST00000488058.1	n.312+5081T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112548 AN: 152014 Hom.: 41731 Cov.: 33

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.741 AC: 112677 AN: 152132 Hom.: 41794 Cov.: 33 AF XY: 0.739 AC XY: 54953 AN XY: 74386

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.722

Alfa AF: 0.739 Hom.: 70200

Bravo AF: 0.735

Asia WGS AF: 0.724 AC: 2519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.79
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs954779; hg19: chr9-36419529;