rs1203847

chr4-2515720-G-Achr4-2515720-G-Cchr4-2515720-G-T

Variant summary

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

The NM_002938.5(RNF4):c.*1901G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.962 in 152,720 control chromosomes in the GnomAD database, including 70,704 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 0.96 (70491 hom., cov: 32)
  • Exomes 𝑓: 0.99 (213 hom.)
• Consequence: RNF4 NM_002938.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF4	NM_002938.5	c.*1901G>A		3_prime_UTR_variant	8/8	ENST00000314289.13
RNF4	NM_001185009.3	c.*1901G>A		3_prime_UTR_variant	9/9
RNF4	NM_001185010.3	c.*1972G>A		3_prime_UTR_variant	7/7
RNF4	XM_047416062.1	c.*1901G>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF4	ENST00000314289.13	c.*1901G>A		3_prime_UTR_variant	8/8	1	NM_002938.5	P1
RNF4	ENST00000541204.5	c.*1972G>A		3_prime_UTR_variant	7/7	1
RNF4	ENST00000511600.5	c.*1901G>A		3_prime_UTR_variant	8/8	2		P1

Frequencies

GnomAD3 genomes AF: 0.962 AC: 146358 AN: 152170 Hom.: 70437 Cov.: 32

Gnomad AFR AF: 0.932

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.984

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.963

GnomAD4 exome AF: 0.993 AC: 429 AN: 432 Hom.: 213 Cov.: 0 AF XY: 0.992 AC XY: 258 AN XY: 260

Gnomad4 FIN exome AF: 0.993

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.962 AC: 146471 AN: 152288 Hom.: 70491 Cov.: 32 AF XY: 0.962 AC XY: 71633 AN XY: 74462

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.972

Gnomad4 ASJ AF: 0.984

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.976

Gnomad4 OTH AF: 0.963

Alfa AF: 0.972 Hom.: 89652

Bravo AF: 0.959

Asia WGS AF: 0.926 AC: 3221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.51
Dann	Benign	0.70

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: rs1203847; hg19: chr4-2517447;