rs1058166

Variant names:

• chr17-37686988-T-C
• rs1058166
• NM_000458.4:c.*384A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000458.4(HNF1B):​c.*384A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 461,494 control chromosomes in the GnomAD database, including 5,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (4424 hom., cov: 32)
  • Exomes 𝑓: 0.068 (1522 hom.)
• Consequence: HNF1B NM_000458.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0240
• Publications: 12 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: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Orphanet
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 17-37686988-T-C is Benign according to our data. Variant chr17-37686988-T-C is described in ClinVar as Benign. ClinVar VariationId is 322938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

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.*384A>G		3_prime_UTR	Exon 9 of 9	NP_000449.1	P35680-1
	HNF1B	NM_001411100.1		c.*292A>G		3_prime_UTR	Exon 8 of 8	NP_001398029.1	A0A087WZC2
	HNF1B	NM_001165923.4		c.*384A>G		3_prime_UTR	Exon 9 of 9	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.*384A>G		3_prime_UTR	Exon 9 of 9	ENSP00000480291.1	P35680-1
	HNF1B	ENST00000904917.1		c.*384A>G		3_prime_UTR	Exon 9 of 9	ENSP00000574976.1
	HNF1B	ENST00000904916.1		c.*384A>G		3_prime_UTR	Exon 8 of 8	ENSP00000574975.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25629 AN: 152070 Hom.: 4411 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0904

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.0680 AC: 21029 AN: 309306 Hom.: 1522 Cov.: 0 AF XY: 0.0655 AC XY: 10712 AN XY: 163458

African (AFR) AF: 0.440 AC: 4048 AN: 9208

American (AMR) AF: 0.0716 AC: 1024 AN: 14304

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 596 AN: 9200

East Asian (EAS) AF: 0.0000535 AC: 1 AN: 18680

South Asian (SAS) AF: 0.0460 AC: 1886 AN: 40966

European-Finnish (FIN) AF: 0.0502 AC: 822 AN: 16360

Middle Eastern (MID) AF: 0.112 AC: 144 AN: 1290

European-Non Finnish (NFE) AF: 0.0602 AC: 10957 AN: 181884

Other (OTH) AF: 0.0891 AC: 1551 AN: 17414

GnomAD4 genome AF: 0.169 AC: 25687 AN: 152188 Hom.: 4424 Cov.: 32 AF XY: 0.165 AC XY: 12296 AN XY: 74412

African (AFR) AF: 0.446 AC: 18487 AN: 41476

American (AMR) AF: 0.0902 AC: 1380 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5178

South Asian (SAS) AF: 0.0381 AC: 184 AN: 4826

European-Finnish (FIN) AF: 0.0623 AC: 661 AN: 10612

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.0620 AC: 4218 AN: 68020

Other (OTH) AF: 0.155 AC: 326 AN: 2108

Alfa AF: 0.109 Hom.: 4614

Bravo AF: 0.184

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Maturity onset diabetes mellitus in young (1)
-	-	1	not provided (1)
-	-	1	Renal cysts and diabetes syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.2
DANN	Benign	0.68
PhyloP100		-0.024
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: rs1058166; hg19: chr17-36046991;