rs7281019

chr21-32586037-T-C

Variant summary

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

The NR_146638.2(CFAP298-TCP10L):n.801-3622A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,146 control chromosomes in the GnomAD database, including 5,063 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 0.24 (5063 hom., cov: 32)
• Consequence: CFAP298-TCP10L NR_146638.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

Genes affected

CFAP298-TCP10L (HGNC:):

TCP10L (HGNC:11657): (t-complex 10 like) Enables several functions, including identical protein binding activity; protein self-association; and transcription corepressor activity. Involved in negative regulation of transcription by RNA polymerase II. Located 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP298-TCP10L	NR_146638.2	n.801-3622A>G		intron_variant, non_coding_transcript_variant
CFAP298-TCP10L	NM_001350338.2	c.667-3622A>G		intron_variant
CFAP298-TCP10L	NR_146639.2	n.801-3622A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCP10L	ENST00000582575.2	c.-2+1276A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36249 AN: 152028 Hom.: 5042 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0865

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.239 AC: 36307 AN: 152146 Hom.: 5063 Cov.: 32 AF XY: 0.234 AC XY: 17431 AN XY: 74392

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.0867

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.256

Alfa AF: 0.199 Hom.: 4102

Bravo AF: 0.243

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.2
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7281019; hg19: chr21-33958347;