12-106696423-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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:58967):

LOC100287944 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213594.3. 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
	RFX4	NM_213594.3	MANE Select	c.810T>C	p.Thr270Thr	synonymous	Exon 8 of 18	NP_998759.1	Q33E94-1
	RFX4	NM_001206691.2		c.837T>C	p.Thr279Thr	synonymous	Exon 8 of 18	NP_001193620.1	Q33E94-2
	RFX4	NM_032491.6		c.528T>C	p.Thr176Thr	synonymous	Exon 4 of 14	NP_115880.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX4	ENST00000392842.6	TSL:1 MANE Select	c.810T>C	p.Thr270Thr	synonymous	Exon 8 of 18	ENSP00000376585.1	Q33E94-1
	RFX4	ENST00000357881.8	TSL:1	c.837T>C	p.Thr279Thr	synonymous	Exon 8 of 18	ENSP00000350552.4	Q33E94-2
	RFX4	ENST00000229387.6	TSL:1	c.528T>C	p.Thr176Thr	synonymous	Exon 4 of 14	ENSP00000229387.5	Q33E94-3

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

GnomAD2 exomes AF: 0.378 AC: 95035 AN: 251318 AF XY: 0.378

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 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

African (AFR) AF: 0.516 AC: 17277 AN: 33480

American (AMR) AF: 0.373 AC: 16680 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.452 AC: 11815 AN: 26136

East Asian (EAS) AF: 0.329 AC: 13056 AN: 39700

South Asian (SAS) AF: 0.392 AC: 33795 AN: 86258

European-Finnish (FIN) AF: 0.286 AC: 15289 AN: 53404

Middle Eastern (MID) AF: 0.415 AC: 2391 AN: 5768

European-Non Finnish (NFE) AF: 0.369 AC: 410246 AN: 1111964

Other (OTH) AF: 0.381 AC: 22982 AN: 60394

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

African (AFR) AF: 0.510 AC: 21123 AN: 41426

American (AMR) AF: 0.369 AC: 5631 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1591 AN: 3472

East Asian (EAS) AF: 0.338 AC: 1744 AN: 5166

South Asian (SAS) AF: 0.402 AC: 1933 AN: 4806

European-Finnish (FIN) AF: 0.281 AC: 2965 AN: 10570

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24879 AN: 67930

Other (OTH) AF: 0.386 AC: 816 AN: 2112

Alfa AF: 0.382 Hom.: 17617

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		-4.1
Mutation Taster		=99/1	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: rs10778502; hg19: chr12-107090201; COSMIC: COSV57576769; COSMIC: COSV57576769;