chr3-71198153-A-G

Position:

• chr3-71198153-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001349338.3(FOXP1):​c.180+49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,662 control chromosomes in the GnomAD database, including 24,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3363 hom., cov: 32)
  • Exomes 𝑓: 0.15 (20716 hom.)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.947

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]

ENSG00000285708 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-71198153-A-G is Benign according to our data. Variant chr3-71198153-A-G is described in ClinVar as [Benign]. Clinvar id is 1273741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.180+49T>C		intron_variant		ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.180+49T>C		intron_variant			NM_001349338.3	ENSP00000497369.1
ENSG00000285708	ENST00000647725.1	c.180+49T>C		intron_variant				ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29390 AN: 152142 Hom.: 3370 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.177

GnomAD3 exomes AF: 0.210 AC: 52567 AN: 250828 Hom.: 7444 AF XY: 0.200 AC XY: 27193 AN XY: 135698

Gnomad AFR exome AF: 0.272

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.404

Gnomad SAS exome AF: 0.250

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.152 AC: 221904 AN: 1461402 Hom.: 20716 Cov.: 35 AF XY: 0.153 AC XY: 111427 AN XY: 727024

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.388

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.350

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.193 AC: 29400 AN: 152260 Hom.: 3363 Cov.: 32 AF XY: 0.196 AC XY: 14587 AN XY: 74450

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.175

Alfa AF: 0.145 Hom.: 2639

Bravo AF: 0.208

Asia WGS AF: 0.324 AC: 1126 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.10
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs2037474; hg19: chr3-71247304; COSMIC: COSV59521684;