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. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 17 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079668.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX2-1	NM_001079668.3	MANE Select	c.77+326_77+329delCTCT		intron	N/A	NP_001073136.1	P43699-3
	NKX2-1-AS1	NR_103710.1		n.402+57_402+60delAGAG		intron	N/A
	NKX2-1	NM_003317.4		c.-370_-367delCTCT		upstream_gene	N/A	NP_003308.1	P43699-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKX2-1	ENST00000354822.7	TSL:1 MANE Select	c.77+326_77+329delCTCT		intron	N/A	ENSP00000346879.6	P43699-3
	NKX2-1	ENST00000522719.4	TSL:1	c.-158-115_-158-112delCTCT		intron	N/A	ENSP00000429519.4	P43699-1
	SFTA3	ENST00000546983.2	TSL:4	n.-13-357_-13-354delCTCT		intron	N/A	ENSP00000449302.2	F8VVG2

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

African (AFR) AF: 0.000578 AC: 17 AN: 29432

American (AMR) AF: 0.000188 AC: 6 AN: 31992

Ashkenazi Jewish (ASJ) AF: 0.0000442 AC: 1 AN: 22606

East Asian (EAS) AF: 0.000127 AC: 4 AN: 31526

South Asian (SAS) AF: 0.000854 AC: 62 AN: 72562

European-Finnish (FIN) AF: 0.000102 AC: 3 AN: 29376

Middle Eastern (MID) AF: 0.000755 AC: 4 AN: 5296

European-Non Finnish (NFE) AF: 0.000109 AC: 111 AN: 1019894

Other (OTH) AF: 0.000354 AC: 19 AN: 53650

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

African (AFR) AF: 0.000242 AC: 10 AN: 41358

American (AMR) AF: 0.00 AC: 0 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.000625 AC: 3 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10284

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67666

Other (OTH) AF: 0.00 AC: 0 AN: 2096

Alfa AF: 0.00 Hom.: 34

Bravo AF: 0.000110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs149047715; hg19: chr14-36988928;