7-114087728-G-A

Variant names:

• chr7-114087728-G-A
• rs6961558
• ENST00000440349.5:n.-247+1117G>A

Variant summary

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

The ENST00000440349.5(FOXP2):​n.-247+1117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 151,458 control chromosomes in the GnomAD database, including 499 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 0.054 (499 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXP2 ENST00000440349.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP2	NR_033766.2	n.285+1117G>A		intron_variant	Intron 1 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP2	ENST00000440349.5	n.-247+1117G>A		intron_variant	Intron 1 of 11	1		ENSP00000395552.1
FOXP2	ENST00000703616.1	c.-357G>A		5_prime_UTR_variant	Exon 1 of 21			ENSP00000515400.1
FOXP2	ENST00000703613.1	c.-365+1117G>A		intron_variant	Intron 1 of 20			ENSP00000515397.1

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 8119 AN: 151340 Hom.: 499 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0362

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.000974

Gnomad SAS AF: 0.0218

Gnomad FIN AF: 0.00369

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0554

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 10

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 14

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0536 AC: 8124 AN: 151458 Hom.: 499 Cov.: 31 AF XY: 0.0520 AC XY: 3849 AN XY: 74064

African (AFR) AF: 0.152 AC: 6302 AN: 41380

American (AMR) AF: 0.0361 AC: 550 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3468

East Asian (EAS) AF: 0.000977 AC: 5 AN: 5120

South Asian (SAS) AF: 0.0214 AC: 103 AN: 4818

European-Finnish (FIN) AF: 0.00369 AC: 38 AN: 10308

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0135 AC: 913 AN: 67844

Other (OTH) AF: 0.0548 AC: 115 AN: 2098

Alfa AF: 0.0221 Hom.: 56

Bravo AF: 0.0595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.4
DANN	Benign	0.93
PhyloP100		-0.045
PromoterAI		0.0042	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6961558; hg19: chr7-113727783;