rs386134268

Variant names:

• chr17-37687401-AGA-G
• rs386134268
• NM_000458.4:c.1654-11_1654-9delTCTinsC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000458.4(HNF1B):​c.1654-11_1654-9delTCTinsC variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 4.16
• Publications: 0 publications found

Genes affected

HNF1B (HGNC:11630): (HNF1 homeobox B) This gene encodes a member of the homeodomain-containing superfamily of transcription factors. The protein binds to DNA as either a homodimer, or a heterodimer with the related protein hepatocyte nuclear factor 1-alpha. The gene has been shown to function in nephron development, and regulates development of the embryonic pancreas. Mutations in this gene result in renal cysts and diabetes syndrome and noninsulin-dependent diabetes mellitus, and expression of this gene is altered in some types of cancer. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

HNF1B Gene-Disease associations (from GenCC):

• renal cysts and diabetes syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet, ClinGen
• diabetes mellitus, noninsulin-dependent

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• permanent neonatal diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• transient neonatal diabetes mellitus

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• medullary sponge kidney

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• renal dysplasia, bilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• renal dysplasia, unilateral

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• renal hypomagnesemia 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• unilateral multicystic dysplastic kidney

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000277688 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000458.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1B	NM_000458.4	MANE Select	c.1654-11_1654-9delTCTinsC		intron	N/A	NP_000449.1	P35680-1
	HNF1B	NM_001411100.1		c.1535-11_1535-9delTCTinsC		intron	N/A	NP_001398029.1	A0A087WZC2
	HNF1B	NM_001165923.4		c.1576-11_1576-9delTCTinsC		intron	N/A	NP_001159395.1	E0YMJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1B	ENST00000617811.5	TSL:1 MANE Select	c.1654-11_1654-9delTCTinsC		intron	N/A	ENSP00000480291.1	P35680-1
	HNF1B	ENST00000621123.4	TSL:1	c.1576-11_1576-9delTCTinsC		intron	N/A	ENSP00000482711.1	P35680-2
	HNF1B	ENST00000613727.4	TSL:1	c.1262-11_1262-9delTCTinsC		intron	N/A	ENSP00000477524.1	A0A0C4DGS8

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Maturity-onset diabetes of the young (1)
-	1	-	not specified (1)
-	1	-	Renal cysts and diabetes syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2

Splicing

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

Other links and lift over

dbSNP: rs386134268; hg19: chr17-36047404;