rs339331

Positions:

• chr6-116888889-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_173560.4(RFX6):​c.567-5098T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,934 control chromosomes in the GnomAD database, including 6,395 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 0.29 (6395 hom., cov: 32)
• Consequence: RFX6 NM_173560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFX6	NM_173560.4	c.567-5098T>C		intron_variant		ENST00000332958.3	NP_775831.2
RFX6	XM_011535589.2	c.567-5098T>C		intron_variant			XP_011533891.1
RFX6	XM_017010477.2	c.189-5098T>C		intron_variant			XP_016865966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFX6	ENST00000332958.3	c.567-5098T>C		intron_variant		1	NM_173560.4	ENSP00000332208	P1
RFX6	ENST00000471966.1	n.257+3844T>C		intron_variant, non_coding_transcript_variant		5
RFX6	ENST00000487683.5	n.631-5098T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43344 AN: 151816 Hom.: 6388 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.286 AC: 43383 AN: 151934 Hom.: 6395 Cov.: 32 AF XY: 0.289 AC XY: 21453 AN XY: 74256

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.252

Alfa AF: 0.293 Hom.: 13883

Bravo AF: 0.275

Asia WGS AF: 0.395 AC: 1374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Benign	0.89

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: rs339331; hg19: chr6-117210052; COSMIC: COSV60586208;