17-37738049-A-G

Variant names:

• chr17-37738049-A-G
• rs4430796
• NM_000458.4:c.544+1391T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000458.4(HNF1B):​c.544+1391T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,996 control chromosomes in the GnomAD database, including 20,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (20898 hom., cov: 32)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.110
• Publications: 399 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-37738049-A-G is Benign according to our data. Variant chr17-37738049-A-G is described in ClinVar as Benign. ClinVar VariationId is 1687622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1B	NM_000458.4	MANE Select	c.544+1391T>C		intron	N/A	NP_000449.1
	HNF1B	NM_001411100.1		c.544+1391T>C		intron	N/A	NP_001398029.1
	HNF1B	NM_001165923.4		c.544+1391T>C		intron	N/A	NP_001159395.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1B	ENST00000617811.5	TSL:1 MANE Select	c.544+1391T>C		intron	N/A	ENSP00000480291.1
	HNF1B	ENST00000621123.4	TSL:1	c.544+1391T>C		intron	N/A	ENSP00000482711.1
	HNF1B	ENST00000613727.4	TSL:1	c.544+1391T>C		intron	N/A	ENSP00000477524.1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77588 AN: 151878 Hom.: 20865 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.511 AC: 77664 AN: 151996 Hom.: 20898 Cov.: 32 AF XY: 0.500 AC XY: 37114 AN XY: 74280

African (AFR) AF: 0.665 AC: 27568 AN: 41438

American (AMR) AF: 0.460 AC: 7018 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 1996 AN: 3462

East Asian (EAS) AF: 0.292 AC: 1507 AN: 5154

South Asian (SAS) AF: 0.353 AC: 1702 AN: 4820

European-Finnish (FIN) AF: 0.341 AC: 3603 AN: 10568

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32450 AN: 67974

Other (OTH) AF: 0.516 AC: 1089 AN: 2110

Alfa AF: 0.491 Hom.: 68949

Bravo AF: 0.528

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Maturity onset diabetes mellitus in young (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs4430796; hg19: chr17-36098040;