12-106608780-C-CTT

Position:

• chr12-106608780-C-CTT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_213594.3(RFX4):​c.44-4_44-3dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00097 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RFX4 NM_213594.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.526

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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 12-106608780-C-CTT is Benign according to our data. Variant chr12-106608780-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 3042661.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAdExome4 at 1231 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFX4	NM_213594.3	c.44-4_44-3dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000392842.6
LOC100287944	NR_040246.1	n.143-100971_143-100970insAA		intron_variant, non_coding_transcript_variant
RFX4	NM_001206691.2	c.71-4_71-3dup		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFX4	ENST00000392842.6	c.44-4_44-3dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_213594.3	P1
	ENST00000551505.4	n.230-108599_230-108598insAA		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 143726 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000966 AC: 1231 AN: 1274724 Hom.: 0 Cov.: 0 AF XY: 0.00101 AC XY: 643 AN XY: 634904

Gnomad4 AFR exome AF: 0.000762

Gnomad4 AMR exome AF: 0.00251

Gnomad4 ASJ exome AF: 0.00140

Gnomad4 EAS exome AF: 0.00170

Gnomad4 SAS exome AF: 0.00272

Gnomad4 FIN exome AF: 0.00118

Gnomad4 NFE exome AF: 0.000759

Gnomad4 OTH exome AF: 0.000960

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 143726 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 69746

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

RFX4-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 19, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs55993073; hg19: chr12-107002558;