rs10511017

Variant names:

• chr3-71360861-T-C
• rs10511017
• NM_001349338.3:c.-167-1617A>G

Variant summary

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

The NM_001349338.3(FOXP1):​c.-167-1617A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,198 control chromosomes in the GnomAD database, including 2,139 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 0.16 (2139 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.990
• 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=-0.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349338.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	NM_001349338.3	MANE Select	c.-167-1617A>G		intron	N/A	NP_001336267.1
	FOXP1	NM_001244810.2		c.-167-1617A>G		intron	N/A	NP_001231739.1
	FOXP1	NM_001244816.2		c.-167-1617A>G		intron	N/A	NP_001231745.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.-167-1617A>G		intron	N/A	ENSP00000497369.1
	FOXP1	ENST00000318789.11	TSL:1	c.-167-1617A>G		intron	N/A	ENSP00000318902.5
	ENSG00000285708	ENST00000647725.1		c.-289-1617A>G		intron	N/A	ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24300 AN: 152078 Hom.: 2135 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.160 AC: 24314 AN: 152196 Hom.: 2139 Cov.: 32 AF XY: 0.157 AC XY: 11698 AN XY: 74408

African (AFR) AF: 0.123 AC: 5125 AN: 41540

American (AMR) AF: 0.130 AC: 1987 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3466

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5186

South Asian (SAS) AF: 0.122 AC: 586 AN: 4818

European-Finnish (FIN) AF: 0.173 AC: 1828 AN: 10584

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.202 AC: 13727 AN: 67992

Other (OTH) AF: 0.155 AC: 327 AN: 2108

Alfa AF: 0.186 Hom.: 4584

Bravo AF: 0.155

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		0.99
PromoterAI		-0.024	Neutral
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: rs10511017; hg19: chr3-71410012;