chr12-106601349-A-G

Position:

• chr12-106601349-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The ENST00000357881.8(RFX4):​c.70+3A>G variant causes a splice donor 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. 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 ENST00000357881.8 splice_donor_region, intron
• Scores: Splicing: ADA: 0.02036
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.45

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 -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 id is 719284.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 539 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFX4	NM_213594.3	c.44-7448A>G		intron_variant		ENST00000392842.6
LOC100287944	NR_040246.1	n.143-93539T>C		intron_variant, non_coding_transcript_variant
RFX4	NM_001206691.2	c.70+3A>G		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFX4	ENST00000392842.6	c.44-7448A>G		intron_variant		1	NM_213594.3	P1
	ENST00000551505.4	n.230-101167T>C		intron_variant, non_coding_transcript_variant		4

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

GnomAD3 exomes AF: 0.00361 AC: 691 AN: 191440 Hom.: 1 AF XY: 0.00378 AC XY: 389 AN XY: 102826

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 SAS exome AF: 0.00237

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

Gnomad4 AFR exome AF: 0.000738

Gnomad4 AMR exome AF: 0.00187

Gnomad4 ASJ exome AF: 0.0115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00192

Gnomad4 FIN exome AF: 0.00306

Gnomad4 NFE exome AF: 0.00482

Gnomad4 OTH exome AF: 0.00440

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

Gnomad4 AFR AF: 0.000649

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.00548

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00549 Hom.: 1

Bravo AF: 0.00409

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.95

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

Publications

LitVar

Other links and lift over

dbSNP: rs113553192; hg19: chr12-106995127;