3-70955638-T-TA

Variant names:

• chr3-70955638-T-TA
• rs533607618
• NM_001349338.3:c.*3608dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001349338.3(FOXP1):​c.*3608dupT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00389 in 233,496 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (1 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.31
• 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 -10 ACMG points.

• BP6: Variant 3-70955638-T-TA is Benign according to our data. Variant chr3-70955638-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 346556.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00358 (545/152194) while in subpopulation SAS AF = 0.0147 (71/4818). AF 95% confidence interval is 0.012. There are 4 homozygotes in GnomAd4. There are 276 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 545 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.*3608dupT		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.*3608dupT		3_prime_UTR_variant	Exon 21 of 21		NM_001349338.3	ENSP00000497369.1
FOXP1	ENST00000318789.11	c.*3608dupT		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000318902.5

Frequencies

GnomAD3 genomes AF: 0.00359 AC: 546 AN: 152076 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.00302

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00515

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.00448 AC: 364 AN: 81302 Hom.: 1 Cov.: 0 AF XY: 0.00489 AC XY: 183 AN XY: 37416

African (AFR) AF: 0.000257 AC: 1 AN: 3894

American (AMR) AF: 0.00 AC: 0 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.00898 AC: 46 AN: 5120

East Asian (EAS) AF: 0.00 AC: 0 AN: 11378

South Asian (SAS) AF: 0.0214 AC: 15 AN: 702

European-Finnish (FIN) AF: 0.00881 AC: 4 AN: 454

Middle Eastern (MID) AF: 0.0102 AC: 5 AN: 492

European-Non Finnish (NFE) AF: 0.00522 AC: 261 AN: 49990

Other (OTH) AF: 0.00473 AC: 32 AN: 6772

GnomAD4 genome AF: 0.00358 AC: 545 AN: 152194 Hom.: 4 Cov.: 32 AF XY: 0.00371 AC XY: 276 AN XY: 74416

African (AFR) AF: 0.000723 AC: 30 AN: 41514

American (AMR) AF: 0.000786 AC: 12 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4818

European-Finnish (FIN) AF: 0.00302 AC: 32 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00515 AC: 350 AN: 68012

Other (OTH) AF: 0.00380 AC: 8 AN: 2108

Alfa AF: 0.00432 Hom.: 0

Bravo AF: 0.00297

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual Disability with Language Impairment and Autistic Features Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3
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: rs533607618; hg19: chr3-71004789;