chr17-37686448-G-C

Variant names:

• chr17-37686448-G-C
• rs10962
• NM_000458.4:c.*924C>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000458.4(HNF1B):​c.*924C>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 0.223 in 151,952 control chromosomes in the GnomAD database, including 3,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3991 hom., cov: 31)
  • Exomes 𝑓: 0.23 (1 hom.)
• Consequence: HNF1B NM_000458.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.44
• Publications: 15 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: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Orphanet
• 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 17-37686448-G-C is Benign according to our data. Variant chr17-37686448-G-C is described in ClinVar as Benign. ClinVar VariationId is 322927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.326 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1B	NM_000458.4	MANE Select	c.*924C>G		3_prime_UTR	Exon 9 of 9	NP_000449.1	P35680-1
	HNF1B	NM_001411100.1		c.*832C>G		3_prime_UTR	Exon 8 of 8	NP_001398029.1	A0A087WZC2
	HNF1B	NM_001165923.4		c.*924C>G		3_prime_UTR	Exon 9 of 9	NP_001159395.1	E0YMJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF1B	ENST00000617811.5	TSL:1 MANE Select	c.*924C>G		3_prime_UTR	Exon 9 of 9	ENSP00000480291.1	P35680-1
	HNF1B	ENST00000904917.1		c.*924C>G		3_prime_UTR	Exon 9 of 9	ENSP00000574976.1
	HNF1B	ENST00000904916.1		c.*924C>G		3_prime_UTR	Exon 8 of 8	ENSP00000574975.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33797 AN: 151812 Hom.: 3984 Cov.: 31

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.227 AC: 5 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.214 AC XY: 3 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.227 AC: 5 AN: 22

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.223 AC: 33819 AN: 151930 Hom.: 3991 Cov.: 31 AF XY: 0.225 AC XY: 16730 AN XY: 74274

African (AFR) AF: 0.187 AC: 7750 AN: 41418

American (AMR) AF: 0.334 AC: 5100 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1372 AN: 5172

South Asian (SAS) AF: 0.218 AC: 1047 AN: 4800

European-Finnish (FIN) AF: 0.229 AC: 2412 AN: 10554

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14940 AN: 67934

Other (OTH) AF: 0.193 AC: 408 AN: 2112

Alfa AF: 0.237 Hom.: 591

Bravo AF: 0.228

Asia WGS AF: 0.231 AC: 806 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Renal cysts and diabetes syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs10962; hg19: chr17-36046451;