20-3958493-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134337.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF24	NM_001134337.3	MANE Select	c.143+5382A>G		intron	N/A	NP_001127809.1
	RNF24	NM_001134338.3		c.206+5382A>G		intron	N/A	NP_001127810.1
	RNF24	NM_001321749.2		c.143+5382A>G		intron	N/A	NP_001308678.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF24	ENST00000358395.11	TSL:1 MANE Select	c.143+5382A>G		intron	N/A	ENSP00000351166.6
	RNF24	ENST00000545616.2	TSL:1	c.206+5382A>G		intron	N/A	ENSP00000444711.1
	RNF24	ENST00000336095.10	TSL:1	c.143+5382A>G		intron	N/A	ENSP00000336753.5

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

African (AFR) AF: 0.666 AC: 27608 AN: 41462

American (AMR) AF: 0.620 AC: 9476 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2625 AN: 3470

East Asian (EAS) AF: 0.567 AC: 2932 AN: 5170

South Asian (SAS) AF: 0.810 AC: 3909 AN: 4828

European-Finnish (FIN) AF: 0.727 AC: 7685 AN: 10578

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49873 AN: 68004

Other (OTH) AF: 0.681 AC: 1440 AN: 2116

Alfa AF: 0.720 Hom.: 171552

Bravo AF: 0.686

Asia WGS AF: 0.706 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.1
DANN	Benign	0.66
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2253977; hg19: chr20-3939140;