rs77390484

Positions:

• chr7-114194735-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000440349.5(FOXP2):​c.-102+31647T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 152,222 control chromosomes in the GnomAD database, including 43 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 0.019 (43 hom., cov: 32)
• Consequence: FOXP2 ENST00000440349.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0187 (2844/152222) while in subpopulation NFE AF= 0.0322 (2186/67970). AF 95% confidence interval is 0.031. There are 43 homozygotes in gnomad4. There are 1322 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2844 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP2	NR_033766.2	n.286-93284T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP2	ENST00000440349.5	c.-102+31647T>C		intron_variant, NMD_transcript_variant		1		ENSP00000395552
FOXP2	ENST00000634411.1	c.-102+31647T>C		intron_variant		5		ENSP00000489135
FOXP2	ENST00000635638.1	c.-102+31647T>C		intron_variant		5		ENSP00000489073

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2842 AN: 152104 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.00565

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.0108

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0321

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0187 AC: 2844 AN: 152222 Hom.: 43 Cov.: 32 AF XY: 0.0178 AC XY: 1322 AN XY: 74420

Gnomad4 AFR AF: 0.00563

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0101

Gnomad4 FIN AF: 0.0108

Gnomad4 NFE AF: 0.0322

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0240 Hom.: 4

Bravo AF: 0.0183

Asia WGS AF: 0.00698 AC: 24 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77390484; hg19: chr7-113834790;