chr17-37687305-C-G

Variant names:

• chr17-37687305-C-G
• rs765609943
• ENST00000613727.4:c.1349G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001411100.1(HNF1B):​c.1622G>C​(p.Gly541Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/11 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: 0.0000027 (0 hom.)
• Consequence: HNF1B NM_001411100.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22755939).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1B	NM_000458.4	c.*67G>C		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.1349G>C	p.Gly450Ala	missense_variant	Exon 7 of 7	1		ENSP00000477524.1
HNF1B	ENST00000617811	c.*67G>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_000458.4	ENSP00000480291.1
HNF1B	ENST00000621123	c.*67G>C		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000482711.1
HNF1B	ENST00000614313.4	c.1622G>C	p.Gly541Ala	missense_variant	Exon 8 of 8	5		ENSP00000482529.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461606 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.67
DEOGEN2	Benign	0.086	T;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.40	N
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Pathogenic	1.1	D
Sift4G	Pathogenic	0.0	D;.
Vest4		0.19
MVP		0.45
ClinPred		0.14	T
GERP RS		2.5

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: rs765609943; hg19: chr17-36047308;