rs2688

Variant names:

• chr17-37686928-T-C
• rs2688
• NM_000458.4:c.*444A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-37686928-T-C
• chr17-37686928-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000458.4(HNF1B):​c.*444A>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 0.00000546 in 183,118 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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>G		3_prime_UTR	Exon 9 of 9	NP_000449.1
	HNF1B	NM_001411100.1		c.*352A>G		3_prime_UTR	Exon 8 of 8	NP_001398029.1
	HNF1B	NM_001165923.4		c.*444A>G		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>G		3_prime_UTR	Exon 9 of 9	ENSP00000480291.1
	ENSG00000277688	ENST00000717158.1		n.981-89T>C		intron	N/A
	ENSG00000277688	ENST00000732653.1		n.252-89T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000546 AC: 1 AN: 183118 Hom.: 0 Cov.: 0 AF XY: 0.0000104 AC XY: 1 AN XY: 96430

African (AFR) AF: 0.00 AC: 0 AN: 6142

American (AMR) AF: 0.00 AC: 0 AN: 8426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5056

East Asian (EAS) AF: 0.00 AC: 0 AN: 9750

South Asian (SAS) AF: 0.00 AC: 0 AN: 26856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 710

European-Non Finnish (NFE) AF: 0.00000930 AC: 1 AN: 107510

Other (OTH) AF: 0.00 AC: 0 AN: 10040

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 28175

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.4
PhyloP100		-0.027

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: rs2688; hg19: chr17-36046931;