Variant 14-36519418-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The ENST00000498187.6(NKX2-1):c.-61C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00607 in 1,607,598 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0062 ( 47 hom. )

Consequence

NKX2-1
ENST00000498187.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.50

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 14-36519418-G-A is Benign according to our data. Variant chr14-36519418-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1186928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00526 (801/152376) while in subpopulation SAS AF= 0.013 (63/4830). AF 95% confidence interval is 0.0105. There are 3 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 801 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
NKX2-1	NM_001079668.3 linkuse as main transcript	c.78-48C>T	intron_variant		ENST00000354822.7	NP_001073136.1
NKX2-1-AS1	NR_103710.1 linkuse as main transcript	n.141G>A	non_coding_transcript_exon_variant	1/2
SFTA3	NR_161364.1 linkuse as main transcript	n.89+50C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKX2-1	ENST00000354822.7 linkuse as main transcript	c.78-48C>T	intron_variant		1	NM_001079668.3	ENSP00000346879	P4	P43699-3
NKX2-1-AS1	ENST00000521292.2 linkuse as main transcript	n.141G>A	non_coding_transcript_exon_variant	1/2	2
	ENST00000634305.1 linkuse as main transcript	n.322+70581G>A	intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00526

AC:

801

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000964

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00704

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00632

AC:

1461

AN:

231156

Hom.:

AF XY:

0.00664

AC XY:

844

AN XY:

127072

show subpopulations

Gnomad AFR exome

AF:

0.00132

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00156

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.0150

Gnomad NFE exome

AF:

0.00703

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

AF:

0.00615

AC:

8956

AN:

1455222

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

4474

AN XY:

723228

show subpopulations

Gnomad4 AFR exome

AF:

0.000659

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.00181

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.00617

Gnomad4 OTH exome

AF:

0.00552

GnomAD4 genome

AF:

0.00526

AC:

801

AN:

152376

Hom.:

Cov.:

AF XY:

0.00569

AC XY:

424

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0130

Gnomad4 FIN

AF:

0.0130

Gnomad4 NFE

AF:

0.00704

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00570

Hom.:

Bravo

AF:

0.00389

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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