chr17-37686928-T-G

Variant names:

• chr17-37686928-T-G
• rs2688
• NM_000458.4:c.*444A>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.*444A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 334,674 control chromosomes in the GnomAD database, including 28,935 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 0.42 (13215 hom., cov: 32)
  • Exomes 𝑓: 0.41 (15720 hom.)
• Consequence: HNF1B NM_000458.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• 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

ENSG00000277688 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.48 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.*444A>C		3_prime_UTR	Exon 9 of 9	NP_000449.1
	HNF1B	NM_001411100.1		c.*352A>C		3_prime_UTR	Exon 8 of 8	NP_001398029.1
	HNF1B	NM_001165923.4		c.*444A>C		3_prime_UTR	Exon 9 of 9	NP_001159395.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1B	ENST00000617811.5	TSL:1 MANE Select	c.*444A>C		3_prime_UTR	Exon 9 of 9	ENSP00000480291.1
	ENSG00000277688	ENST00000717158.1		n.981-89T>G		intron	N/A
	ENSG00000277688	ENST00000732653.1		n.252-89T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63056 AN: 151858 Hom.: 13201 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.398

GnomAD4 exome AF: 0.406 AC: 74213 AN: 182698 Hom.: 15720 Cov.: 0 AF XY: 0.407 AC XY: 39198 AN XY: 96202

African (AFR) AF: 0.438 AC: 2686 AN: 6130

American (AMR) AF: 0.508 AC: 4276 AN: 8412

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1695 AN: 5046

East Asian (EAS) AF: 0.417 AC: 4062 AN: 9734

South Asian (SAS) AF: 0.422 AC: 11304 AN: 26794

European-Finnish (FIN) AF: 0.420 AC: 3611 AN: 8596

Middle Eastern (MID) AF: 0.429 AC: 303 AN: 706

European-Non Finnish (NFE) AF: 0.395 AC: 42322 AN: 107258

Other (OTH) AF: 0.395 AC: 3954 AN: 10022

GnomAD4 genome AF: 0.415 AC: 63113 AN: 151976 Hom.: 13215 Cov.: 32 AF XY: 0.417 AC XY: 30997 AN XY: 74286

African (AFR) AF: 0.435 AC: 18023 AN: 41418

American (AMR) AF: 0.489 AC: 7471 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1172 AN: 3468

East Asian (EAS) AF: 0.410 AC: 2125 AN: 5184

South Asian (SAS) AF: 0.418 AC: 2009 AN: 4810

European-Finnish (FIN) AF: 0.417 AC: 4397 AN: 10550

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.391 AC: 26580 AN: 67958

Other (OTH) AF: 0.399 AC: 843 AN: 2112

Alfa AF: 0.398 Hom.: 28175

Bravo AF: 0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.1
PhyloP100		-0.027

Splicing

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

Other links and lift over

dbSNP: rs2688; hg19: chr17-36046931;