6-116920858-T-C

Position:

• chr6-116920858-T-C

Variant summary

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

The NM_173560.4(RFX6):​c.1327+404T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,972 control chromosomes in the GnomAD database, including 7,495 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 0.31 (7495 hom., cov: 32)
• Consequence: RFX6 NM_173560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

Genes affected

RFX6 (HGNC:21478): (regulatory factor X6) The nuclear protein encoded by this gene is a member of the regulatory factor X (RFX) family of transcription factors. Studies in mice suggest that this gene is specifically required for the differentiation of islet cells for the production of insulin, but not for the differentiation of pancreatic polypeptide-producing cells. It regulates the transcription factors involved in beta-cell maturation and function, thus, restricting the expression of the beta-cell differentiation and specification genes. Mutations in this gene are associated with Mitchell-Riley syndrome, which is characterized by neonatal diabetes with pancreatic hypoplasia, duodenal and jejunal atresia, and gall bladder agenesis.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFX6	NM_173560.4	c.1327+404T>C		intron_variant		ENST00000332958.3
RFX6	XM_011535589.2	c.1219+404T>C		intron_variant
RFX6	XM_017010477.2	c.949+404T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFX6	ENST00000332958.3	c.1327+404T>C		intron_variant		1	NM_173560.4	P1
RFX6	ENST00000487683.5	n.1391+404T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47080 AN: 151854 Hom.: 7480 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.310 AC: 47139 AN: 151972 Hom.: 7495 Cov.: 32 AF XY: 0.315 AC XY: 23374 AN XY: 74302

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.283

Alfa AF: 0.303 Hom.: 1204

Bravo AF: 0.301

Asia WGS AF: 0.454 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.73

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: rs12202378; hg19: chr6-117242021; COSMIC: COSV60588683; COSMIC: COSV60588683;