NM_001349338.3:c.*3414_*3415insTGTGTGTGCG

Variant names:

• chr3-70955832-G-GCGCACACACA
• rs1553648184
• NM_001349338.3:c.*3414_*3415insTGTGTGTGCG

Variant summary

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

The NM_001349338.3(FOXP1):​c.*3414_*3415insTGTGTGTGCG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 221,622 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 26)
  • Exomes 𝑓: 0.00069 (0 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373

Genes affected

FOXP1 (HGNC:3823): (forkhead box P1) This gene belongs to subfamily P of the forkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. Forkhead box P1 protein contains both DNA-binding- and protein-protein binding-domains. This gene may act as a tumor suppressor as it is lost in several tumor types and maps to a chromosomal region (3p14.1) reported to contain a tumor suppressor gene(s). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00261 (385/147258) while in subpopulation AFR AF= 0.00859 (347/40402). AF 95% confidence interval is 0.00784. There are 2 homozygotes in gnomad4. There are 174 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 385 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.*3414_*3415insTGTGTGTGCG		3_prime_UTR_variant	Exon 21 of 21	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528	c.*3414_*3415insTGTGTGTGCG		3_prime_UTR_variant	Exon 21 of 21		NM_001349338.3	ENSP00000497369.1
FOXP1	ENST00000318789	c.*3414_*3415insTGTGTGTGCG		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000318902.5

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 386 AN: 147162 Hom.: 2 Cov.: 26

Gnomad AFR AF: 0.00864

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000796

Gnomad SAS AF: 0.000645

Gnomad FIN AF: 0.000314

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000151

Gnomad OTH AF: 0.000988

GnomAD4 exome AF: 0.000686 AC: 51 AN: 74364 Hom.: 0 Cov.: 0 AF XY: 0.000644 AC XY: 22 AN XY: 34160

Gnomad4 AFR exome AF: 0.00840

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000362

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000133

Gnomad4 OTH exome AF: 0.000651

GnomAD4 genome AF: 0.00261 AC: 385 AN: 147258 Hom.: 2 Cov.: 26 AF XY: 0.00243 AC XY: 174 AN XY: 71616

Gnomad4 AFR AF: 0.00859

Gnomad4 AMR AF: 0.00109

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000797

Gnomad4 SAS AF: 0.000647

Gnomad4 FIN AF: 0.000314

Gnomad4 NFE AF: 0.000151

Gnomad4 OTH AF: 0.000978

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: rs1553648184; hg19: chr3-71004983;