12-106696423-T-C

Variant names:

• chr12-106696423-T-C
• rs10778502
• NM_213594.3:c.810T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_213594.3(RFX4):​c.810T>C​(p.Thr270Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,613,776 control chromosomes in the GnomAD database, including 115,197 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 0.40 (12711 hom., cov: 31)
  • Exomes 𝑓: 0.37 (102486 hom.)
• Consequence: RFX4 NM_213594.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.06

Genes affected

RFX4 (HGNC:9985): (regulatory factor X4) This gene is a member of the regulatory factor X gene family, which encodes transcription factors that contain a highly-conserved winged helix DNA binding domain. The protein encoded by this gene is structurally related to regulatory factors X1, X2, X3, and X5. It has been shown to interact with itself as well as with regulatory factors X2 and X3, but it does not interact with regulatory factor X1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

ENSG00000257545 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-4.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFX4	NM_213594.3	c.810T>C	p.Thr270Thr	synonymous_variant	Exon 8 of 18	ENST00000392842.6	NP_998759.1
RFX4	NM_001206691.2	c.837T>C	p.Thr279Thr	synonymous_variant	Exon 8 of 18		NP_001193620.1
RFX4	NM_032491.6	c.528T>C	p.Thr176Thr	synonymous_variant	Exon 4 of 14		NP_115880.2
LOC100287944	NR_040246.1	n.142+78267A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFX4	ENST00000392842.6	c.810T>C	p.Thr270Thr	synonymous_variant	Exon 8 of 18	1	NM_213594.3	ENSP00000376585.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61094 AN: 151834 Hom.: 12687 Cov.: 31

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.391

GnomAD3 exomes AF: 0.378 AC: 95035 AN: 251318 Hom.: 18464 AF XY: 0.378 AC XY: 51335 AN XY: 135834

Gnomad AFR exome AF: 0.516

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.454

Gnomad EAS exome AF: 0.349

Gnomad SAS exome AF: 0.390

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.370

Gnomad OTH exome AF: 0.385

GnomAD4 exome AF: 0.372 AC: 543531 AN: 1461824 Hom.: 102486 Cov.: 48 AF XY: 0.373 AC XY: 270941 AN XY: 727224

Gnomad4 AFR exome AF: 0.516

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.392

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.381

GnomAD4 genome AF: 0.402 AC: 61155 AN: 151952 Hom.: 12711 Cov.: 31 AF XY: 0.398 AC XY: 29566 AN XY: 74294

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.386

Alfa AF: 0.377 Hom.: 13858

Bravo AF: 0.418

Asia WGS AF: 0.353 AC: 1230 AN: 3478

EpiCase AF: 0.390

EpiControl AF: 0.395

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.52

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: rs10778502; hg19: chr12-107090201; COSMIC: COSV57576769; COSMIC: COSV57576769;