chr17-37704890-A-G

Position:

• chr17-37704890-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000458.4(HNF1B):​c.1339+27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,612,856 control chromosomes in the GnomAD database, including 12,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (724 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11357 hom.)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.629

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-37704890-A-G is Benign according to our data. Variant chr17-37704890-A-G is described in ClinVar as [Benign]. Clinvar id is 1279728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF1B	NM_000458.4	c.1339+27T>C		intron_variant		ENST00000617811.5	NP_000449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF1B	ENST00000617811.5	c.1339+27T>C		intron_variant		1	NM_000458.4	ENSP00000480291.1
HNF1B	ENST00000621123.4	c.1261+27T>C		intron_variant		1		ENSP00000482711.1
HNF1B	ENST00000613727.4	c.1261+27T>C		intron_variant		1		ENSP00000477524.1
HNF1B	ENST00000614313.4	c.1339+27T>C		intron_variant		5		ENSP00000482529.1

Frequencies

GnomAD3 genomes AF: 0.0872 AC: 13260 AN: 152080 Hom.: 724 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0697

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0727

Gnomad FIN AF: 0.0854

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.0975

GnomAD3 exomes AF: 0.0919 AC: 23102 AN: 251464 Hom.: 1281 AF XY: 0.0965 AC XY: 13109 AN XY: 135912

Gnomad AFR exome AF: 0.0282

Gnomad AMR exome AF: 0.0492

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.0794

Gnomad FIN exome AF: 0.0813

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.119 AC: 173695 AN: 1460658 Hom.: 11357 Cov.: 32 AF XY: 0.119 AC XY: 86253 AN XY: 726728

Gnomad4 AFR exome AF: 0.0276

Gnomad4 AMR exome AF: 0.0523

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.0778

Gnomad4 FIN exome AF: 0.0794

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.0871 AC: 13253 AN: 152198 Hom.: 724 Cov.: 32 AF XY: 0.0842 AC XY: 6263 AN XY: 74426

Gnomad4 AFR AF: 0.0302

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0723

Gnomad4 FIN AF: 0.0854

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.0960

Alfa AF: 0.120 Hom.: 488

Bravo AF: 0.0829

Asia WGS AF: 0.0270 AC: 96 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.11
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs2107133; hg19: chr17-36064897;