3-70965870-G-T

Variant names:

• chr3-70965870-G-T
• rs7638391
• NM_001349338.3:c.1889+20C>A

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.1889+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 1,612,816 control chromosomes in the GnomAD database, including 694,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68269 hom., cov: 30)
  • Exomes 𝑓: 0.93 (625832 hom.)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.57
• Publications: 14 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=-0.91).
• BP6: Variant 3-70965870-G-T is Benign according to our data. Variant chr3-70965870-G-T is described in ClinVar as Benign. ClinVar VariationId is 96228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.1889+20C>A		intron	N/A	NP_001336267.1	Q548T7
	FOXP1	NM_001244810.2		c.1937+20C>A		intron	N/A	NP_001231739.1	Q9H334-8
	FOXP1	NM_001244814.3		c.1889+20C>A		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.1889+20C>A		intron	N/A	ENSP00000497369.1	Q9H334-1
	FOXP1	ENST00000318789.11	TSL:1	c.1889+20C>A		intron	N/A	ENSP00000318902.5	Q9H334-1
	ENSG00000285708	ENST00000647725.1		c.1889+20C>A		intron	N/A	ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.947 AC: 143909 AN: 152028 Hom.: 68210 Cov.: 30

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.943

GnomAD2 exomes AF: 0.945 AC: 237666 AN: 251442 AF XY: 0.944

Gnomad AFR exome AF: 0.987

Gnomad AMR exome AF: 0.963

Gnomad ASJ exome AF: 0.915

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.944

Gnomad NFE exome AF: 0.921

Gnomad OTH exome AF: 0.940

GnomAD4 exome AF: 0.925 AC: 1351559 AN: 1460670 Hom.: 625832 Cov.: 40 AF XY: 0.927 AC XY: 673551 AN XY: 726672

African (AFR) AF: 0.987 AC: 33018 AN: 33456

American (AMR) AF: 0.963 AC: 43059 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 23918 AN: 26128

East Asian (EAS) AF: 1.00 AC: 39692 AN: 39698

South Asian (SAS) AF: 0.972 AC: 83836 AN: 86216

European-Finnish (FIN) AF: 0.946 AC: 50530 AN: 53416

Middle Eastern (MID) AF: 0.928 AC: 4791 AN: 5162

European-Non Finnish (NFE) AF: 0.915 AC: 1016888 AN: 1111580

Other (OTH) AF: 0.926 AC: 55827 AN: 60290

GnomAD4 genome AF: 0.947 AC: 144027 AN: 152146 Hom.: 68269 Cov.: 30 AF XY: 0.949 AC XY: 70578 AN XY: 74374

African (AFR) AF: 0.985 AC: 40873 AN: 41516

American (AMR) AF: 0.943 AC: 14424 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3171 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5149 AN: 5150

South Asian (SAS) AF: 0.974 AC: 4689 AN: 4812

European-Finnish (FIN) AF: 0.948 AC: 10039 AN: 10590

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.920 AC: 62581 AN: 68006

Other (OTH) AF: 0.944 AC: 1986 AN: 2104

Alfa AF: 0.935 Hom.: 13650

Bravo AF: 0.948

Asia WGS AF: 0.987 AC: 3428 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Intellectual disability-severe speech delay-mild dysmorphism syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.015
DANN	Benign	0.34
PhyloP100		-1.6
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7638391; hg19: chr3-71015021; COSMIC: COSV59535400; COSMIC: COSV59535400;