chr12-120996827-C-CTCATTCATTCAT

Position:

• chr12-120996827-C-CTCATTCATTCAT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000545.8(HNF1A):​c.1309+90_1309+101dupTCATTCATTCAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000736 in 1,530,548 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00076 (3 hom.)
• Consequence: HNF1A NM_000545.8 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.434

Genes affected

HNF1A (HGNC:11621): (HNF1 homeobox A) The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

HNF1A (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 76 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF1A	NM_000545.8	c.1309+90_1309+101dupTCATTCATTCAT		intron_variant		ENST00000257555.11	NP_000536.6
HNF1A	NM_001306179.2	c.1309+90_1309+101dupTCATTCATTCAT		intron_variant			NP_001293108.2
HNF1A	NM_001406915.1	c.1309+90_1309+101dupTCATTCATTCAT		intron_variant			NP_001393844.1
HNF1A	XM_024449168.2	c.1309+90_1309+101dupTCATTCATTCAT		intron_variant			XP_024304936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF1A	ENST00000257555.11	c.1309+90_1309+101dupTCATTCATTCAT		intron_variant		1	NM_000545.8	ENSP00000257555.5

Frequencies

GnomAD3 genomes AF: 0.000504 AC: 76 AN: 150776 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00138

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.000191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000710

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000654 AC: 100 AN: 152926 Hom.: 2 AF XY: 0.000733 AC XY: 60 AN XY: 81904

Gnomad AFR exome AF: 0.000118

Gnomad AMR exome AF: 0.000455

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00226

Gnomad SAS exome AF: 0.000444

Gnomad FIN exome AF: 0.000197

Gnomad NFE exome AF: 0.000802

Gnomad OTH exome AF: 0.000457

GnomAD4 exome AF: 0.000762 AC: 1051 AN: 1379654 Hom.: 3 Cov.: 39 AF XY: 0.000773 AC XY: 527 AN XY: 681742

Gnomad4 AFR exome AF: 0.000221

Gnomad4 AMR exome AF: 0.000364

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00282

Gnomad4 SAS exome AF: 0.000634

Gnomad4 FIN exome AF: 0.000103

Gnomad4 NFE exome AF: 0.000776

Gnomad4 OTH exome AF: 0.000820

GnomAD4 genome AF: 0.000504 AC: 76 AN: 150894 Hom.: 0 Cov.: 0 AF XY: 0.000489 AC XY: 36 AN XY: 73694

Gnomad4 AFR AF: 0.000268

Gnomad4 AMR AF: 0.000198

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00138

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.000191

Gnomad4 NFE AF: 0.000710

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000139 Hom.: 4223

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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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: rs58371019; hg19: chr12-121434630;