4-2512457-G-A

Variant names:

• chr4-2512457-G-A
• rs377600326
• NM_002938.5:c.234G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002938.5(RNF4):​c.234G>A​(p.Arg78Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF4 NM_002938.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.824
• Publications: 0 publications found

Genes affected

RNF4 (HGNC:10067): (ring finger protein 4) The protein encoded by this gene contains a RING finger motif and acts as a transcription regulator. This protein has been shown to interact with, and inhibit the activity of, TRPS1, a transcription suppressor of GATA-mediated transcription. Transcription repressor ZNF278/PATZ is found to interact with this protein, and thus reduce the enhancement of androgen receptor-dependent transcription mediated by this protein. Studies of the mouse and rat counterparts suggested a role of this protein in spermatogenesis. A pseudogene of this gene is found on chromosome 1.[provided by RefSeq, Jul 2010]

ENSG00000290180 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=0.824 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002938.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF4	NM_002938.5	MANE Select	c.234G>A	p.Arg78Arg	synonymous	Exon 6 of 8	NP_002929.1	P78317-1
	RNF4	NM_001185009.3		c.234G>A	p.Arg78Arg	synonymous	Exon 7 of 9	NP_001171938.1	P78317-1
	RNF4	NM_001185010.3		c.214+492G>A		intron	N/A	NP_001171939.1	P78317-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF4	ENST00000314289.13	TSL:1 MANE Select	c.234G>A	p.Arg78Arg	synonymous	Exon 6 of 8	ENSP00000315212.8	P78317-1
	RNF4	ENST00000506706.5	TSL:1	c.234G>A	p.Arg78Arg	synonymous	Exon 7 of 9	ENSP00000424076.1	P78317-1
	RNF4	ENST00000511859.5	TSL:1	c.214+492G>A		intron	N/A	ENSP00000426615.1	P78317-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460076 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726190

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 85986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111158

Other (OTH) AF: 0.00 AC: 0 AN: 60312

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.3
DANN	Benign	0.56
PhyloP100		0.82

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: rs377600326; hg19: chr4-2514184;