chr3-70955834-A-G

Variant names:

• chr3-70955834-A-G
• rs185295985
• NM_001349338.3:c.*3413T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001349338.3(FOXP1):​c.*3413T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 163,854 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (5 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.435
• Publications: 0 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 3-70955834-A-G is Benign according to our data. Variant chr3-70955834-A-G is described in ClinVar as [Benign]. Clinvar id is 1695077.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.*3413T>C		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	ENST00000649528.3	c.*3413T>C		3_prime_UTR_variant	Exon 21 of 21		NM_001349338.3	ENSP00000497369.1
FOXP1	ENST00000318789.11	c.*3413T>C		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000318902.5

Frequencies

GnomAD3 genomes AF: 0.00776 AC: 1117 AN: 144004 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.0344

Gnomad AMR AF: 0.00761

Gnomad ASJ AF: 0.00177

Gnomad EAS AF: 0.000397

Gnomad SAS AF: 0.00323

Gnomad FIN AF: 0.00526

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0133

GnomAD4 exome AF: 0.0340 AC: 672 AN: 19774 Hom.: 1 Cov.: 0 AF XY: 0.0367 AC XY: 325 AN XY: 8866

African (AFR) AF: 0.00910 AC: 17 AN: 1868

American (AMR) AF: 0.0276 AC: 15 AN: 544

Ashkenazi Jewish (ASJ) AF: 0.0106 AC: 10 AN: 946

East Asian (EAS) AF: 0.000604 AC: 3 AN: 4970

South Asian (SAS) AF: 0.00500 AC: 1 AN: 200

European-Finnish (FIN) AF: 0.0196 AC: 2 AN: 102

Middle Eastern (MID) AF: 0.0104 AC: 1 AN: 96

European-Non Finnish (NFE) AF: 0.0583 AC: 553 AN: 9488

Other (OTH) AF: 0.0449 AC: 70 AN: 1560

GnomAD4 genome AF: 0.00775 AC: 1116 AN: 144080 Hom.: 5 Cov.: 32 AF XY: 0.00737 AC XY: 518 AN XY: 70256

African (AFR) AF: 0.00382 AC: 143 AN: 37434

American (AMR) AF: 0.00760 AC: 111 AN: 14610

Ashkenazi Jewish (ASJ) AF: 0.00177 AC: 6 AN: 3384

East Asian (EAS) AF: 0.000398 AC: 2 AN: 5022

South Asian (SAS) AF: 0.00324 AC: 15 AN: 4634

European-Finnish (FIN) AF: 0.00526 AC: 52 AN: 9880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.0111 AC: 730 AN: 65972

Other (OTH) AF: 0.0132 AC: 26 AN: 1968

Alfa AF: 0.00801 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FOXP1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.10
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism

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: rs185295985; hg19: chr3-71004985;