12-120997672-G-C

Position:

• chr12-120997672-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000545.8(HNF1A):​c.1501+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HNF1A NM_000545.8 splice_region, intron
• Scores: Splicing: ADA: 0.000009096
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055052012).
• BP6: Variant 12-120997672-G-C is Benign according to our data. Variant chr12-120997672-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 747559.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1A	NM_000545.8	c.1501+7G>C		splice_region_variant, intron_variant		ENST00000257555.11
HNF1A	NM_001306179.2	c.1501+7G>C		splice_region_variant, intron_variant
HNF1A	NM_001406915.1	c.1309+930G>C		intron_variant
HNF1A	XM_024449168.2	c.1501+7G>C		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1A	ENST00000257555.11	c.1501+7G>C		splice_region_variant, intron_variant		1	NM_000545.8	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.035
DANN	Benign	0.46
DEOGEN2	Benign	0.23	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P
Sift4G	Benign	0.18	T
Vest4		0.10
MVP		0.40
ClinPred		0.097	T
GERP RS		-9.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000091
dbscSNV1_RF	Benign	0.0
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: rs2464195; hg19: chr12-121435475;