rs113553192

Variant names:

• chr12-106601349-A-G
• rs113553192
• NM_213594.3:c.44-7448A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001206691.2(RFX4):​c.70+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,578,056 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0044 (24 hom.)
• Consequence: RFX4 NM_001206691.2 splice_region, intron
• Scores: Splicing: ADA: 0.02036
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.45
• Publications: 0 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:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 12-106601349-A-G is Benign according to our data. Variant chr12-106601349-A-G is described in ClinVar as Benign. ClinVar VariationId is 719284.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 539 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206691.2. 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.44-7448A>G		intron	N/A	NP_998759.1	Q33E94-1
	RFX4	NM_001206691.2		c.70+3A>G		splice_region intron	N/A	NP_001193620.1	Q33E94-2
	LOC100287944	NR_040246.1		n.143-93539T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX4	ENST00000392842.6	TSL:1 MANE Select	c.44-7448A>G		intron	N/A	ENSP00000376585.1	Q33E94-1
	RFX4	ENST00000357881.8	TSL:1	c.70+3A>G		splice_region intron	N/A	ENSP00000350552.4	Q33E94-2
	RFX4	ENST00000536688.5	TSL:1	n.175+3A>G		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00354 AC: 539 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00548

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00361 AC: 691 AN: 191440 AF XY: 0.00378

Gnomad AFR exome AF: 0.000813

Gnomad AMR exome AF: 0.00100

Gnomad ASJ exome AF: 0.00965

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00252

Gnomad NFE exome AF: 0.00553

Gnomad OTH exome AF: 0.00474

GnomAD4 exome AF: 0.00438 AC: 6247 AN: 1425734 Hom.: 24 Cov.: 31 AF XY: 0.00432 AC XY: 3054 AN XY: 706142

African (AFR) AF: 0.000738 AC: 24 AN: 32518

American (AMR) AF: 0.00187 AC: 77 AN: 41120

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 293 AN: 25576

East Asian (EAS) AF: 0.00 AC: 0 AN: 37928

South Asian (SAS) AF: 0.00192 AC: 157 AN: 81730

European-Finnish (FIN) AF: 0.00306 AC: 156 AN: 50948

Middle Eastern (MID) AF: 0.00274 AC: 12 AN: 4378

European-Non Finnish (NFE) AF: 0.00482 AC: 5269 AN: 1092738

Other (OTH) AF: 0.00440 AC: 259 AN: 58798

GnomAD4 genome AF: 0.00354 AC: 539 AN: 152322 Hom.: 0 Cov.: 33 AF XY: 0.00337 AC XY: 251 AN XY: 74488

African (AFR) AF: 0.000649 AC: 27 AN: 41586

American (AMR) AF: 0.00405 AC: 62 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00548 AC: 373 AN: 68028

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00549 Hom.: 1

Bravo AF: 0.00409

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.95
PhyloP100		3.5
PromoterAI		-0.087	Neutral
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.020
dbscSNV1_RF	Benign	0.036
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: rs113553192; hg19: chr12-106995127;