rs7616330

Variant names:

• chr3-71066600-C-A
• rs7616330
• NM_001349338.3:c.283-12827G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-71066600-C-A
• chr3-71066600-C-T

Variant summary

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

The NM_001349338.3(FOXP1):​c.283-12827G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,118 control chromosomes in the GnomAD database, including 3,448 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 0.19 (3448 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.553 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.283-12827G>T		intron	N/A	NP_001336267.1	Q548T7
	FOXP1	NM_001244810.2		c.283-12827G>T		intron	N/A	NP_001231739.1	Q9H334-8
	FOXP1	NM_001244814.3		c.283-12827G>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.283-12827G>T		intron	N/A	ENSP00000497369.1	Q9H334-1
	FOXP1	ENST00000318789.11	TSL:1	c.283-12827G>T		intron	N/A	ENSP00000318902.5	Q9H334-1
	ENSG00000285708	ENST00000647725.1		c.283-12827G>T		intron	N/A	ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29411 AN: 152000 Hom.: 3441 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.179

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29449 AN: 152118 Hom.: 3448 Cov.: 32 AF XY: 0.202 AC XY: 15018 AN XY: 74374

African (AFR) AF: 0.169 AC: 7010 AN: 41490

American (AMR) AF: 0.162 AC: 2484 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 321 AN: 3470

East Asian (EAS) AF: 0.570 AC: 2948 AN: 5168

South Asian (SAS) AF: 0.389 AC: 1874 AN: 4822

European-Finnish (FIN) AF: 0.259 AC: 2738 AN: 10580

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11543 AN: 67978

Other (OTH) AF: 0.183 AC: 386 AN: 2112

Alfa AF: 0.170 Hom.: 1666

Bravo AF: 0.186

Asia WGS AF: 0.491 AC: 1706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		0.58
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: rs7616330; hg19: chr3-71115751;