Variant 14-36516974-CA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001079668.3(NKX2-1):c.*303del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 447,900 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000076 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

NKX2-1
NM_001079668.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.798

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 14-36516974-CA-C is Benign according to our data. Variant chr14-36516974-CA-C is described in ClinVar as [Benign]. Clinvar id is 2431068.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000076 (11/144650) while in subpopulation AFR AF= 0.000122 (5/41080). AF 95% confidence interval is 0.0000477. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
NKX2-1	NM_001079668.3 linkuse as main transcript	c.*303del	3_prime_UTR_variant	3/3	ENST00000354822.7
SFTA3	NR_161364.1 linkuse as main transcript	n.89+2493del	intron_variant, non_coding_transcript_variant
NKX2-1	NM_003317.4 linkuse as main transcript	c.*303del	3_prime_UTR_variant	2/2
SFTA3	NR_161365.1 linkuse as main transcript	n.89+2493del	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKX2-1	ENST00000354822.7 linkuse as main transcript	c.*303del	3_prime_UTR_variant	3/3	1	NM_001079668.3	P4	P43699-3
NKX2-1	ENST00000498187.6 linkuse as main transcript	c.*303del	3_prime_UTR_variant	2/2	1		A1	P43699-1
	ENST00000634305.1 linkuse as main transcript	n.322+68144del	intron_variant, non_coding_transcript_variant		5
NKX2-1	ENST00000518149.5 linkuse as main transcript	c.*303del	3_prime_UTR_variant	3/3	5		A1	P43699-1

Frequencies

GnomAD3 genomes

AF:

0.0000760

AC:

AN:

144650

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000410

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000315

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000119

AC:

AN:

303250

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

155942

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000973

Gnomad4 EAS exome

AF:

0.000108

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00183

Gnomad4 NFE exome

AF:

0.0000314

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000760

AC:

AN:

144650

Hom.:

Cov.:

AF XY:

0.0000852

AC XY:

AN XY:

70440

show subpopulations

Gnomad4 AFR

AF:

0.000122

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000410

Gnomad4 NFE

AF:

0.0000315

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lung adenocarcinoma

Benign:1

Benign, criteria provided, single submitter

research

Liquid Biopsy and Cancer Interception Group, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research

Jun 06, 2022

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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