3-71269842-C-T

Variant names:

• chr3-71269842-C-T
• rs2280518
• NM_001349338.3:c.-12+29978G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001349338.3(FOXP1):​c.-12+29978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,030 control chromosomes in the GnomAD database, including 3,678 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 0.18 (3678 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 3 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]

FOXP1 Gene-Disease associations (from GenCC):

• intellectual disability-severe speech delay-mild dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000285708 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.-12+29978G>A		intron_variant	Intron 5 of 20	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.-12+29978G>A		intron_variant	Intron 5 of 20		NM_001349338.3	ENSP00000497369.1
ENSG00000285708	ENST00000647725.1	c.-12+29978G>A		intron_variant	Intron 10 of 25			ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27307 AN: 151914 Hom.: 3672 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0858

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0779

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.180 AC: 27340 AN: 152030 Hom.: 3678 Cov.: 32 AF XY: 0.184 AC XY: 13676 AN XY: 74312

African (AFR) AF: 0.344 AC: 14253 AN: 41426

American (AMR) AF: 0.153 AC: 2343 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0858 AC: 298 AN: 3472

East Asian (EAS) AF: 0.455 AC: 2355 AN: 5172

South Asian (SAS) AF: 0.269 AC: 1294 AN: 4818

European-Finnish (FIN) AF: 0.109 AC: 1147 AN: 10556

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0779 AC: 5299 AN: 67986

Other (OTH) AF: 0.149 AC: 314 AN: 2106

Alfa AF: 0.112 Hom.: 4788

Bravo AF: 0.187

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.69
PhyloP100		1.2
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: rs2280518; hg19: chr3-71318993;