chr3-71477054-G-A

Variant names:

• chr3-71477054-G-A
• rs17108
• NM_001349338.3:c.-168+16372C>T

Variant summary

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

The NM_001349338.3(FOXP1):​c.-168+16372C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,942 control chromosomes in the GnomAD database, including 10,165 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 0.36 (10165 hom., cov: 31)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• 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]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.-168+16372C>T		intron_variant	Intron 3 of 20	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.-168+16372C>T		intron_variant	Intron 3 of 20		NM_001349338.3	ENSP00000497369.1
ENSG00000285708	ENST00000647725.1	c.-290+16372C>T		intron_variant	Intron 7 of 25			ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54291 AN: 151824 Hom.: 10154 Cov.: 31

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.00598

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.358 AC: 54323 AN: 151942 Hom.: 10165 Cov.: 31 AF XY: 0.353 AC XY: 26183 AN XY: 74254

African (AFR) AF: 0.381 AC: 15800 AN: 41428

American (AMR) AF: 0.292 AC: 4461 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1383 AN: 3470

East Asian (EAS) AF: 0.00600 AC: 31 AN: 5168

South Asian (SAS) AF: 0.290 AC: 1400 AN: 4820

European-Finnish (FIN) AF: 0.387 AC: 4071 AN: 10532

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25978 AN: 67938

Other (OTH) AF: 0.358 AC: 754 AN: 2108

Alfa AF: 0.378 Hom.: 2640

Bravo AF: 0.346

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.67
DANN	Benign	0.55
PhyloP100		-1.0
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: rs17108; hg19: chr3-71526205;