rs17006292

Positions:

• chr2-121261187-C-A
• chr2-121261187-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014553.3(TFCP2L1):​c.215-11540G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 152,290 control chromosomes in the GnomAD database, including 143 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 0.028 (143 hom., cov: 33)
• Consequence: TFCP2L1 NM_014553.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFCP2L1	NM_014553.3	c.215-11540G>T		intron_variant		ENST00000263707.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFCP2L1	ENST00000263707.6	c.215-11540G>T		intron_variant		1	NM_014553.3	P1

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4218 AN: 152172 Hom.: 142 Cov.: 33

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0288

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00285

Gnomad OTH AF: 0.0244

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

GnomAD4 genome AF: 0.0279 AC: 4243 AN: 152290 Hom.: 143 Cov.: 33 AF XY: 0.0286 AC XY: 2126 AN XY: 74458

Gnomad4 AFR AF: 0.0842

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0289

Gnomad4 SAS AF: 0.0336

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00285

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.00846 Hom.: 13

Bravo AF: 0.0308

Asia WGS AF: 0.0290 AC: 101 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.43

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: rs17006292; hg19: chr2-122018763;