NM_001349338.3:c.-298+8251T>C

Variant names:

• chr3-71573298-A-G
• rs878172
• NM_001349338.3:c.-298+8251T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349338.3(FOXP1):​c.-298+8251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,420 control chromosomes in the GnomAD database, including 29,477 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (29477 hom., cov: 30)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 5 publications found

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]

ENSG00000285708 (HGNC:):

FOXP1-IT1 (HGNC:41335): (FOXP1 intronic transcript 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.-298+8251T>C		intron_variant	Intron 2 of 20	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.-298+8251T>C		intron_variant	Intron 2 of 20		NM_001349338.3	ENSP00000497369.1
ENSG00000285708	ENST00000647725.1	c.-419-79743T>C		intron_variant	Intron 6 of 25			ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92129 AN: 151302 Hom.: 29450 Cov.: 30

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.612

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.606

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.609 AC: 92197 AN: 151420 Hom.: 29477 Cov.: 30 AF XY: 0.600 AC XY: 44372 AN XY: 73918

African (AFR) AF: 0.689 AC: 28364 AN: 41166

American (AMR) AF: 0.490 AC: 7449 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2203 AN: 3466

East Asian (EAS) AF: 0.0352 AC: 182 AN: 5170

South Asian (SAS) AF: 0.411 AC: 1978 AN: 4816

European-Finnish (FIN) AF: 0.672 AC: 6975 AN: 10376

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.634 AC: 43070 AN: 67916

Other (OTH) AF: 0.599 AC: 1263 AN: 2110

Alfa AF: 0.607 Hom.: 5627

Bravo AF: 0.595

Asia WGS AF: 0.239 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.59
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs878172; hg19: chr3-71622449;