17-37687325-A-T

Variant names:

• chr17-37687325-A-T
• rs8068014
• ENST00000613727.4:c.1329T>A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BS1 BS2

The NM_001411100.1(HNF1B):​c.1602T>A​(p.Phe534Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict 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: 0.000016 (0 hom.)
• Consequence: HNF1B NM_001411100.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2753536).
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000157 (23/1461766) while in subpopulation EAS AF= 0.000579 (23/39700). AF 95% confidence interval is 0.000396. There are 0 homozygotes in gnomad4_exome. There are 13 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1B	NM_000458.4	c.*47T>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000617811.5	NP_000449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF1B	ENST00000613727.4	c.1329T>A	p.Phe443Leu	missense_variant	Exon 7 of 7	1		ENSP00000477524.1
HNF1B	ENST00000617811	c.*47T>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_000458.4	ENSP00000480291.1
HNF1B	ENST00000621123	c.*47T>A		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000482711.1
HNF1B	ENST00000614313.4	c.1602T>A	p.Phe534Leu	missense_variant	Exon 8 of 8	5		ENSP00000482529.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1461766 Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13 AN XY: 727174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000579

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T;T
Eigen	Benign	0.10
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Pathogenic	0.93	D
Sift4G	Benign	0.64	T;T
Vest4		0.25
MVP		0.77
ClinPred		0.80	D
GERP RS		4.9

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: rs8068014; hg19: chr17-36047328;