4-2515720-G-C

Variant names:

• chr4-2515720-G-C
• rs1203847
• NM_002938.5:c.*1901G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002938.5(RNF4):​c.*1901G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: RNF4 NM_002938.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 8 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF4	NM_002938.5	c.*1901G>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000314289.13	NP_002929.1
RNF4	NM_001185009.3	c.*1901G>C		3_prime_UTR_variant	Exon 9 of 9		NP_001171938.1
RNF4	NM_001185010.3	c.*1972G>C		3_prime_UTR_variant	Exon 7 of 7		NP_001171939.1
RNF4	XM_047416062.1	c.*1901G>C		3_prime_UTR_variant	Exon 9 of 9		XP_047272018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF4	ENST00000314289.13	c.*1901G>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_002938.5	ENSP00000315212.8
RNF4	ENST00000541204.5	c.*1972G>C		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000446369.2
ENSG00000290180	ENST00000703446.1	n.296+1923G>C		intron_variant	Intron 3 of 4			ENSP00000515299.1
RNF4	ENST00000511600.5	c.*1901G>C		3_prime_UTR_variant	Exon 8 of 8	2		ENSP00000426503.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.43
DANN	Benign	0.73
PhyloP100		-0.33

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: rs1203847; hg19: chr4-2517447;