rs11868513

Variant names:

• chr17-37692682-G-A
• rs11868513
• NM_000458.4:c.1654-5290C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000458.4(HNF1B):​c.1654-5290C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,204 control chromosomes in the GnomAD database, including 2,521 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 0.17 (2521 hom., cov: 32)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 15 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: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1B	NM_000458.4	c.1654-5290C>T		intron_variant	Intron 8 of 8	ENST00000617811.5	NP_000449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF1B	ENST00000617811.5	c.1654-5290C>T		intron_variant	Intron 8 of 8	1	NM_000458.4	ENSP00000480291.1
HNF1B	ENST00000621123.4	c.1576-5290C>T		intron_variant	Intron 8 of 8	1		ENSP00000482711.1
HNF1B	ENST00000613727.4	c.1262-5290C>T		intron_variant	Intron 6 of 6	1		ENSP00000477524.1
HNF1B	ENST00000614313.4	c.1535-5290C>T		intron_variant	Intron 7 of 7	5		ENSP00000482529.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25194 AN: 152086 Hom.: 2518 Cov.: 32

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.166 AC: 25197 AN: 152204 Hom.: 2521 Cov.: 32 AF XY: 0.168 AC XY: 12491 AN XY: 74412

African (AFR) AF: 0.0477 AC: 1983 AN: 41560

American (AMR) AF: 0.206 AC: 3149 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 746 AN: 3472

East Asian (EAS) AF: 0.258 AC: 1336 AN: 5170

South Asian (SAS) AF: 0.217 AC: 1044 AN: 4822

European-Finnish (FIN) AF: 0.209 AC: 2209 AN: 10580

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.208 AC: 14148 AN: 67998

Other (OTH) AF: 0.183 AC: 386 AN: 2110

Alfa AF: 0.184 Hom.: 5226

Bravo AF: 0.159

Asia WGS AF: 0.259 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.70
PhyloP100		0.021
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11868513; hg19: chr17-36052692;