rs3110641

Variant names:

• chr17-37687414-G-A
• rs3110641
• NM_000458.4:c.1654-22C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-37687414-G-A
• chr17-37687414-G-C
• chr17-37687414-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000458.4(HNF1B):​c.1654-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,583,410 control chromosomes in the GnomAD database, including 53,253 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (9292 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43961 hom.)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 23 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: G2P, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF1B	NM_000458.4	c.1654-22C>T		intron_variant	Intron 8 of 8	ENST00000617811.5	NP_000449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF1B	ENST00000617811.5	c.1654-22C>T		intron_variant	Intron 8 of 8	1	NM_000458.4	ENSP00000480291.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48501 AN: 151832 Hom.: 9261 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.239 AC: 342249 AN: 1431460 Hom.: 43961 Cov.: 26 AF XY: 0.242 AC XY: 172990 AN XY: 713878

African (AFR) AF: 0.555 AC: 18278 AN: 32938

American (AMR) AF: 0.197 AC: 8797 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 7641 AN: 25946

East Asian (EAS) AF: 0.279 AC: 11044 AN: 39530

South Asian (SAS) AF: 0.328 AC: 28078 AN: 85636

European-Finnish (FIN) AF: 0.211 AC: 11183 AN: 52940

Middle Eastern (MID) AF: 0.352 AC: 2009 AN: 5708

European-Non Finnish (NFE) AF: 0.221 AC: 239519 AN: 1084674

Other (OTH) AF: 0.264 AC: 15700 AN: 59406

GnomAD4 genome AF: 0.320 AC: 48588 AN: 151950 Hom.: 9292 Cov.: 32 AF XY: 0.318 AC XY: 23622 AN XY: 74256

African (AFR) AF: 0.540 AC: 22362 AN: 41412

American (AMR) AF: 0.243 AC: 3710 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1208 AN: 5148

South Asian (SAS) AF: 0.311 AC: 1498 AN: 4824

European-Finnish (FIN) AF: 0.211 AC: 2226 AN: 10562

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15534 AN: 67958

Other (OTH) AF: 0.324 AC: 682 AN: 2106

Alfa AF: 0.261 Hom.: 11560

Bravo AF: 0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs3110641; hg19: chr17-36047417;