rs60540213

Variant names:

• chr7-114562406-G-A
• rs60540213
• NM_014491.4:c.258+27700G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-114562406-G-A
• chr7-114562406-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014491.4(FOXP2):​c.258+27700G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0809 in 152,062 control chromosomes in the GnomAD database, including 1,039 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 0.081 (1039 hom., cov: 32)
• Consequence: FOXP2 NM_014491.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 1 publications found

Genes affected

FOXP2 (HGNC:13875): (forkhead box P2) This gene encodes a member of the forkhead/winged-helix (FOX) family of transcription factors. It is expressed in fetal and adult brain as well as in several other organs such as the lung and gut. The protein product contains a FOX DNA-binding domain and a large polyglutamine tract and is an evolutionarily conserved transcription factor, which may bind directly to approximately 300 to 400 gene promoters in the human genome to regulate the expression of a variety of genes. This gene is required for proper development of speech and language regions of the brain during embryogenesis, and may be involved in a variety of biological pathways and cascades that may ultimately influence language development. Mutations in this gene cause speech-language disorder 1 (SPCH1), also known as autosomal dominant speech and language disorder with orofacial dyspraxia. Multiple alternative transcripts encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

FOXP2 Gene-Disease associations (from GenCC):

• specific language disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• childhood apraxia of speech

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014491.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	NM_014491.4	MANE Select	c.258+27700G>A		intron	N/A	NP_055306.1
	FOXP2	NM_148898.4		c.259-8401G>A		intron	N/A	NP_683696.2
	FOXP2	NM_148900.4		c.258+27700G>A		intron	N/A	NP_683698.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP2	ENST00000350908.9	TSL:1 MANE Select	c.258+27700G>A		intron	N/A	ENSP00000265436.7
	FOXP2	ENST00000408937.7	TSL:1	c.259-8401G>A		intron	N/A	ENSP00000386200.3
	FOXP2	ENST00000390668.3	TSL:1	c.256-8401G>A		intron	N/A	ENSP00000375084.3

Frequencies

GnomAD3 genomes AF: 0.0808 AC: 12281 AN: 151944 Hom.: 1037 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0606

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.0701

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

GnomAD4 genome AF: 0.0809 AC: 12309 AN: 152062 Hom.: 1039 Cov.: 32 AF XY: 0.0819 AC XY: 6091 AN XY: 74344

African (AFR) AF: 0.198 AC: 8202 AN: 41440

American (AMR) AF: 0.0607 AC: 928 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3468

East Asian (EAS) AF: 0.234 AC: 1210 AN: 5170

South Asian (SAS) AF: 0.116 AC: 560 AN: 4818

European-Finnish (FIN) AF: 0.0195 AC: 206 AN: 10584

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0126 AC: 857 AN: 67986

Other (OTH) AF: 0.0699 AC: 147 AN: 2104

Alfa AF: 0.0663 Hom.: 118

Bravo AF: 0.0919

Asia WGS AF: 0.168 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.25
PhyloP100		-2.0
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: rs60540213; hg19: chr7-114202461;