Variant chr2-121242351-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014553.3(TFCP2L1):c.768+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,613,436 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 19 hom. )

Consequence

TFCP2L1
NM_014553.3 splice_region, intron

Scores

Splicing: ADA: 0.0002656

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0710

Variant links:

Genes affected

TFCP2L1 (HGNC:17925): (transcription factor CP2 like 1) Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm and membrane. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TFCP2L1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 2-121242351-C-T is Benign according to our data. Variant chr2-121242351-C-T is described in ClinVar as [Benign]. Clinvar id is 780023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00245 (3580/1461138) while in subpopulation MID AF= 0.0281 (162/5768). AF 95% confidence interval is 0.0246. There are 19 homozygotes in gnomad4_exome. There are 1936 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFCP2L1	NM_014553.3 linkuse as main transcript	c.768+8G>A		splice_region_variant, intron_variant		ENST00000263707.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFCP2L1	ENST00000263707.6 linkuse as main transcript	c.768+8G>A		splice_region_variant, intron_variant		1	NM_014553.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00261

AC:

397

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.0360

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00220

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00357

AC:

898

AN:

251354

Hom.:

AF XY:

0.00391

AC XY:

531

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.0362

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00340

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00273

Gnomad OTH exome

AF:

0.00522

GnomAD4 exome

AF:

0.00245

AC:

3580

AN:

1461138

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

1936

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.00271

Gnomad4 ASJ exome

AF:

0.0331

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00295

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00165

Gnomad4 OTH exome

AF:

0.00485

GnomAD4 genome

AF:

0.00259

AC:

395

AN:

152298

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.0360

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00422

Hom.:

Bravo

AF:

0.00275

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00365

EpiControl

AF:

0.00433

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	May 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.4

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00027

dbscSNV1_RF

Benign

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over