17-37720815-A-G

Variant names:

• chr17-37720815-A-G
• rs7407025
• NM_000458.4:c.1046-10152T>C

Variant summary

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

The NM_000458.4(HNF1B):​c.1046-10152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 985,080 control chromosomes in the GnomAD database, including 30,518 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 0.25 (5136 hom., cov: 31)
  • Exomes 𝑓: 0.25 (25382 hom.)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• 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: 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

LOC105371754 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 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.1046-10152T>C		intron	N/A	NP_000449.1
	HNF1B	NM_001411100.1		c.1046-10152T>C		intron	N/A	NP_001398029.1
	HNF1B	NM_001165923.4		c.968-10152T>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.1046-10152T>C		intron	N/A	ENSP00000480291.1
	HNF1B	ENST00000621123.4	TSL:1	c.968-10152T>C		intron	N/A	ENSP00000482711.1
	HNF1B	ENST00000613727.4	TSL:1	c.968-10152T>C		intron	N/A	ENSP00000477524.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38315 AN: 151898 Hom.: 5122 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.245 AC: 204360 AN: 833064 Hom.: 25382 Cov.: 30 AF XY: 0.246 AC XY: 94513 AN XY: 384694

African (AFR) AF: 0.190 AC: 2994 AN: 15786

American (AMR) AF: 0.318 AC: 313 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1803 AN: 5152

East Asian (EAS) AF: 0.278 AC: 1009 AN: 3630

South Asian (SAS) AF: 0.388 AC: 6394 AN: 16460

European-Finnish (FIN) AF: 0.283 AC: 78 AN: 276

Middle Eastern (MID) AF: 0.309 AC: 501 AN: 1620

European-Non Finnish (NFE) AF: 0.242 AC: 184169 AN: 761858

Other (OTH) AF: 0.260 AC: 7099 AN: 27298

GnomAD4 genome AF: 0.252 AC: 38357 AN: 152016 Hom.: 5136 Cov.: 31 AF XY: 0.257 AC XY: 19121 AN XY: 74292

African (AFR) AF: 0.200 AC: 8293 AN: 41478

American (AMR) AF: 0.295 AC: 4497 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1222 AN: 3464

East Asian (EAS) AF: 0.267 AC: 1379 AN: 5162

South Asian (SAS) AF: 0.381 AC: 1835 AN: 4816

European-Finnish (FIN) AF: 0.312 AC: 3291 AN: 10542

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17093 AN: 67980

Other (OTH) AF: 0.251 AC: 530 AN: 2112

Alfa AF: 0.255 Hom.: 11091

Bravo AF: 0.248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.038
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs7407025; hg19: chr17-36080810;