rs149047715

Variant names:

• chr14-36519723-AAGAG-A
• rs149047715
• NM_001079668.3:c.77+326_77+329delCTCT

Your query was ambiguous. Multiple possible variants found:

• chr14-36519723-AAGAG-A
• chr14-36519723-AAGAG-AAG
• chr14-36519723-AAGAG-AAGAGAG
• chr14-36519723-AAGAG-AAGAGAGAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001079668.3(NKX2-1):​c.77+326_77+329delCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,447,520 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: NKX2-1 NM_001079668.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31

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]

SFTA3 (HGNC:):

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

SFTA3 (HGNC:18387): (surfactant associated 3) Involved in wound healing. Located in cytoplasm and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000112 (17/151186) while in subpopulation SAS AF= 0.000625 (3/4800). AF 95% confidence interval is 0.000169. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKX2-1	NM_001079668.3	c.77+326_77+329delCTCT		intron_variant	Intron 1 of 2	ENST00000354822.7	NP_001073136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKX2-1	ENST00000354822.7	c.77+326_77+329delCTCT		intron_variant	Intron 1 of 2	1	NM_001079668.3	ENSP00000346879.6
SFTA3	ENST00000546983.2	n.-13-357_-13-354delCTCT		intron_variant	Intron 1 of 3	4		ENSP00000449302.2

Frequencies

GnomAD3 genomes AF: 0.000106 AC: 16 AN: 151078 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000175 AC: 227 AN: 1296334 Hom.: 0 AF XY: 0.000192 AC XY: 122 AN XY: 635682

Gnomad4 AFR exome AF: 0.000578

Gnomad4 AMR exome AF: 0.000188

Gnomad4 ASJ exome AF: 0.0000442

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.000854

Gnomad4 FIN exome AF: 0.000102

Gnomad4 NFE exome AF: 0.000109

Gnomad4 OTH exome AF: 0.000354

GnomAD4 genome AF: 0.000112 AC: 17 AN: 151186 Hom.: 0 Cov.: 31 AF XY: 0.000122 AC XY: 9 AN XY: 73842

Gnomad4 AFR AF: 0.000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000625

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000296

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000110

ClinVar

Not reported in ClinVar

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: rs149047715; hg19: chr14-36988928;