20-3958493-T-C

Variant names:

• chr20-3958493-T-C
• rs2253977
• NM_001134337.3:c.143+5382A>G

Variant summary

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

The NM_001134337.3(RNF24):​c.143+5382A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,106 control chromosomes in the GnomAD database, including 37,415 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 0.70 (37415 hom., cov: 32)
• Consequence: RNF24 NM_001134337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

Genes affected

RNF24 (HGNC:13779): (ring finger protein 24) This gene encodes an integral membrane protein that contains a RING-type zinc finger. The encoded protein may interact with multiple transient receptor potential cation channel subfamily C (TRPC) proteins and regulate the trafficking and insertion of these proteins into the plasma membrane. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF24	NM_001134337.3	c.143+5382A>G		intron_variant	Intron 2 of 5	ENST00000358395.11	NP_001127809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF24	ENST00000358395.11	c.143+5382A>G		intron_variant	Intron 2 of 5	1	NM_001134337.3	ENSP00000351166.6
RNF24	ENST00000545616.2	c.206+5382A>G		intron_variant	Intron 3 of 6	1		ENSP00000444711.1
RNF24	ENST00000336095.10	c.143+5382A>G		intron_variant	Intron 2 of 5	1		ENSP00000336753.5
RNF24	ENST00000432261.6	c.206+5382A>G		intron_variant	Intron 2 of 5	5		ENSP00000388550.2

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106354 AN: 151988 Hom.: 37382 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.700 AC: 106432 AN: 152106 Hom.: 37415 Cov.: 32 AF XY: 0.698 AC XY: 51877 AN XY: 74338

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.810

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.681

Alfa AF: 0.725 Hom.: 82181

Bravo AF: 0.686

Asia WGS AF: 0.706 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.1
DANN	Benign	0.66

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: rs2253977; hg19: chr20-3939140;