4-2515720-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
RNF4	NM_002938.5	c.*1901G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000314289.13	NP_002929.1
RNF4	NM_001185009.3	c.*1901G>A		3_prime_UTR_variant	Exon 9 of 9		NP_001171938.1
RNF4	NM_001185010.3	c.*1972G>A		3_prime_UTR_variant	Exon 7 of 7		NP_001171939.1
RNF4	XM_047416062.1	c.*1901G>A		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>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_002938.5	ENSP00000315212.8
RNF4	ENST00000541204.5	c.*1972G>A		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000446369.2
ENSG00000290180	ENST00000703446.1	n.296+1923G>A		intron_variant	Intron 3 of 4			ENSP00000515299.1
RNF4	ENST00000511600.5	c.*1901G>A		3_prime_UTR_variant	Exon 8 of 8	2		ENSP00000426503.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.993 AC: 423 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 1.00 AC: 4 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0662318), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.932 AC: 38732 AN: 41544

American (AMR) AF: 0.972 AC: 14855 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.984 AC: 3418 AN: 3472

East Asian (EAS) AF: 0.898 AC: 4661 AN: 5190

South Asian (SAS) AF: 0.953 AC: 4600 AN: 4826

European-Finnish (FIN) AF: 0.996 AC: 10578 AN: 10624

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.976 AC: 66390 AN: 68034

Other (OTH) AF: 0.963 AC: 2035 AN: 2114

Alfa AF: 0.969 Hom.: 129586

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
PhyloP100		-0.33
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: rs1203847; hg19: chr4-2517447;