Variant 14-36519624-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The ENST00000522719.4(NKX2-1):c.-158-12T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,530,792 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 51 hom. )

Consequence

NKX2-1
ENST00000522719.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.57

Variant links:

Genes affected

NKX2-1 (HGNC:11825): (NK2 homeobox 1) This gene encodes a protein initially identified as a thyroid-specific transcription factor. The encoded protein binds to the thyroglobulin promoter and regulates the expression of thyroid-specific genes but has also been shown to regulate the expression of genes involved in morphogenesis. Mutations and deletions in this gene are associated with benign hereditary chorea, choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress, and may be associated with thyroid cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares the symbol/alias 'TTF1' with another gene, transcription termination factor 1, which plays a role in ribosomal gene transcription. [provided by RefSeq, Feb 2014]

NKX2-1 links:

NKX2-1-AS1 (HGNC:40585): (NKX2-1 antisense RNA 1)

NKX2-1-AS1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 14-36519624-A-G is Benign according to our data. Variant chr14-36519624-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1333071.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000998 (152/152364) while in subpopulation SAS AF= 0.0313 (151/4830). AF 95% confidence interval is 0.0272. There are 4 homozygotes in gnomad4. There are 113 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 152 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKX2-1	NM_001079668.3 linkuse as main transcript	c.78-254T>C		intron_variant		ENST00000354822.7	NP_001073136.1
NKX2-1-AS1	NR_103710.1 linkuse as main transcript	n.347A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKX2-1	ENST00000354822.7 linkuse as main transcript	c.78-254T>C	intron_variant		1	NM_001079668.3	ENSP00000346879	P4	P43699-3
NKX2-1-AS1	ENST00000521292.2 linkuse as main transcript	n.347A>G	non_coding_transcript_exon_variant	1/2	2
	ENST00000634305.1 linkuse as main transcript	n.322+70787A>G	intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00100

AC:

153

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0314

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00457

AC:

600

AN:

131330

Hom.:

AF XY:

0.00596

AC XY:

427

AN XY:

71702

show subpopulations

Gnomad AFR exome

AF:

0.000164

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000192

Gnomad SAS exome

AF:

0.0260

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000396

Gnomad OTH exome

AF:

0.00347

GnomAD4 exome

AF:

0.00161

AC:

2215

AN:

1378428

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

1587

AN XY:

679986

show subpopulations

Gnomad4 AFR exome

AF:

0.000222

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000283

Gnomad4 SAS exome

AF:

0.0261

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000836

Gnomad4 OTH exome

AF:

0.00257

GnomAD4 genome

AF:

0.000998

AC:

152

AN:

152364

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0313

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000384

Hom.:

Bravo

AF:

0.000189

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.91

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over