rs7639736

Variant names:

• chr3-70959406-C-A
• rs7639736
• NM_001349338.3:c.1890-15G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-70959406-C-A
• chr3-70959406-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001349338.3(FOXP1):​c.1890-15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,613,826 control chromosomes in the GnomAD database, including 593 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (133 hom., cov: 31)
  • Exomes 𝑓: 0.015 (460 hom.)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.151
• Publications: 9 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina, ClinGen
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000285708 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-70959406-C-A is Benign according to our data. Variant chr3-70959406-C-A is described in ClinVar as Benign. ClinVar VariationId is 1282214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0748 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	NM_001349338.3	MANE Select	c.1890-15G>T		intron	N/A	NP_001336267.1	Q548T7
	FOXP1	NM_001244810.2		c.1938-15G>T		intron	N/A	NP_001231739.1	Q9H334-8
	FOXP1	NM_001244814.3		c.1890-15G>T		intron	N/A	NP_001231743.1	Q9H334-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.1890-15G>T		intron	N/A	ENSP00000497369.1	Q9H334-1
	FOXP1	ENST00000318789.11	TSL:1	c.1890-15G>T		intron	N/A	ENSP00000318902.5	Q9H334-1
	ENSG00000285708	ENST00000647725.1		c.1890-15G>T		intron	N/A	ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5190 AN: 151996 Hom.: 132 Cov.: 31

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0520

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0323

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00831

Gnomad OTH AF: 0.0254

GnomAD2 exomes AF: 0.0285 AC: 7157 AN: 250992 AF XY: 0.0258

Gnomad AFR exome AF: 0.0727

Gnomad AMR exome AF: 0.0631

Gnomad ASJ exome AF: 0.00566

Gnomad EAS exome AF: 0.0720

Gnomad FIN exome AF: 0.0331

Gnomad NFE exome AF: 0.00782

Gnomad OTH exome AF: 0.0248

GnomAD4 exome AF: 0.0147 AC: 21492 AN: 1461712 Hom.: 460 Cov.: 34 AF XY: 0.0146 AC XY: 10594 AN XY: 727148

African (AFR) AF: 0.0692 AC: 2316 AN: 33476

American (AMR) AF: 0.0622 AC: 2782 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00551 AC: 144 AN: 26134

East Asian (EAS) AF: 0.0835 AC: 3314 AN: 39690

South Asian (SAS) AF: 0.0210 AC: 1810 AN: 86252

European-Finnish (FIN) AF: 0.0318 AC: 1699 AN: 53402

Middle Eastern (MID) AF: 0.00747 AC: 43 AN: 5760

European-Non Finnish (NFE) AF: 0.00741 AC: 8243 AN: 1111900

Other (OTH) AF: 0.0189 AC: 1141 AN: 60386

GnomAD4 genome AF: 0.0342 AC: 5202 AN: 152114 Hom.: 133 Cov.: 31 AF XY: 0.0350 AC XY: 2604 AN XY: 74346

African (AFR) AF: 0.0702 AC: 2910 AN: 41460

American (AMR) AF: 0.0520 AC: 794 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.0812 AC: 419 AN: 5158

South Asian (SAS) AF: 0.0201 AC: 97 AN: 4826

European-Finnish (FIN) AF: 0.0323 AC: 342 AN: 10596

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

European-Non Finnish (NFE) AF: 0.00831 AC: 565 AN: 68010

Other (OTH) AF: 0.0256 AC: 54 AN: 2106

Alfa AF: 0.0226 Hom.: 24

Bravo AF: 0.0381

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.39
PhyloP100		0.15
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: rs7639736; hg19: chr3-71008557; COSMIC: COSV107387740;