rs142240844

Positions:

• chr17-37710456-CTCTTA-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP3 BP6 BS2

The NM_000458.4(HNF1B):​c.1206+42_1206+46del variant causes a intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,608,726 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 8.85

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]

LOC124903989 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• BP6: Variant 17-37710456-CTCTTA-C is Benign according to our data. Variant chr17-37710456-CTCTTA-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 447508.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS2: High AC in GnomAd4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF1B	NM_000458.4	c.1206+42_1206+46del		intron_variant		ENST00000617811.5	NP_000449.1
LOC124903989	XR_007065732.1	n.5797_5801del		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF1B	ENST00000617811.5	c.1206+42_1206+46del		intron_variant		1	NM_000458.4	ENSP00000480291
HNF1B	ENST00000613727.4	c.1128+42_1128+46del		intron_variant		1		ENSP00000477524
HNF1B	ENST00000621123.4	c.1128+42_1128+46del		intron_variant		1		ENSP00000482711	P1
HNF1B	ENST00000614313.4	c.1206+42_1206+46del		intron_variant		5		ENSP00000482529

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152186 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000147 AC: 37 AN: 251206 Hom.: 0 AF XY: 0.000169 AC XY: 23 AN XY: 135800

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000133 AC: 194 AN: 1456422 Hom.: 0 AF XY: 0.000123 AC XY: 89 AN XY: 724950

Gnomad4 AFR exome AF: 0.0000899

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.000374

Gnomad4 NFE exome AF: 0.000137

Gnomad4 OTH exome AF: 0.000149

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152304 Hom.: 1 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74476

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000254 Hom.: 0

Bravo AF: 0.000151

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Sep 28, 2018

- -

Maturity onset diabetes mellitus in young Benign:1

Likely benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

-

HNF1B gene mutations are associated with early onset diabetes and pancreatic atrophy. It is also associated with multiple renal manifestations including renal cysts, Tubulointerstitial disease, glomerulocystic disease, renal hypoplasia, hypomagnesemia. However no sufficient evidence is found to ascertain the role of this particular variant rs142240844, yet. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs142240844; hg19: chr17-36070464;