rs2107131

Variant names:

• chr17-37726698-G-A
• rs2107131
• NM_000458.4:c.1045+4897C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-37726698-G-A
• chr17-37726698-G-C
• chr17-37726698-G-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.1045+4897C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,986 control chromosomes in the GnomAD database, including 7,362 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 0.29 (7362 hom., cov: 31)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 9 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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.397 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.1045+4897C>T		intron	N/A	NP_000449.1
	HNF1B	NM_001411100.1		c.1045+4897C>T		intron	N/A	NP_001398029.1
	HNF1B	NM_001165923.4		c.967+4897C>T		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.1045+4897C>T		intron	N/A	ENSP00000480291.1
	HNF1B	ENST00000621123.4	TSL:1	c.967+4897C>T		intron	N/A	ENSP00000482711.1
	HNF1B	ENST00000613727.4	TSL:1	c.967+4897C>T		intron	N/A	ENSP00000477524.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44119 AN: 151868 Hom.: 7348 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.291 AC: 44163 AN: 151986 Hom.: 7362 Cov.: 31 AF XY: 0.298 AC XY: 22121 AN XY: 74270

African (AFR) AF: 0.125 AC: 5201 AN: 41484

American (AMR) AF: 0.405 AC: 6200 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3466

East Asian (EAS) AF: 0.366 AC: 1891 AN: 5166

South Asian (SAS) AF: 0.410 AC: 1966 AN: 4798

European-Finnish (FIN) AF: 0.400 AC: 4216 AN: 10540

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.335 AC: 22782 AN: 67934

Other (OTH) AF: 0.277 AC: 582 AN: 2104

Alfa AF: 0.309 Hom.: 13242

Bravo AF: 0.283

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.9
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs2107131; hg19: chr17-36086689;