12-106755644-A-T

Position:

• chr12-106755644-A-T

Variant summary

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

The NM_213594.3(RFX4):​c.1935+4851A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,112 control chromosomes in the GnomAD database, including 31,235 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 0.62 (31235 hom., cov: 32)
• Consequence: RFX4 NM_213594.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFX4	NM_213594.3	c.1935+4851A>T		intron_variant		ENST00000392842.6
LOC100287944	NR_040246.1	n.142+19046T>A		intron_variant, non_coding_transcript_variant
RFX4	NM_001206691.2	c.1962+4851A>T		intron_variant
RFX4	NM_032491.6	c.1653+4851A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFX4	ENST00000392842.6	c.1935+4851A>T		intron_variant		1	NM_213594.3	P1
	ENST00000551505.4	n.229+19046T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94527 AN: 151994 Hom.: 31177 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.586

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.622 AC: 94642 AN: 152112 Hom.: 31235 Cov.: 32 AF XY: 0.619 AC XY: 46003 AN XY: 74334

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.582

Alfa AF: 0.578 Hom.: 3319

Bravo AF: 0.642

Asia WGS AF: 0.571 AC: 1985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.5
DANN	Benign	0.78

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: rs2067615; hg19: chr12-107149422;