ENST00000673807.1:c.667-3622A>G

Variant names:

• chr21-32586037-T-C
• rs7281019
• ENST00000673807.1:c.667-3622A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000673807.1(CFAP298-TCP10L):​c.667-3622A>G variant causes a intron 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 ENST00000673807.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614
• Publications: 7 publications found

Genes affected

CFAP298-TCP10L (HGNC:54636): (CFAP298-TCP10L readthrough) This locus represents naturally occurring readthrough transcription between the neighboring chromosome 21 open reading frame 59 (C21orf59) and TCP10L (t-complex 10 like) genes on chromosome 21. Readthrough transcripts may encode a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000673807.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP298-TCP10L	NM_001350338.2		c.667-3622A>G		intron	N/A	NP_001337267.1
	CFAP298-TCP10L	NR_146638.2		n.801-3622A>G		intron	N/A
	CFAP298-TCP10L	NR_146639.2		n.801-3622A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP298-TCP10L	ENST00000673807.1		c.667-3622A>G		intron	N/A	ENSP00000501088.1
	CFAP298-TCP10L	ENST00000673985.1		c.667-3622A>G		intron	N/A	ENSP00000500984.1
	CFAP298-TCP10L	ENST00000673945.1		c.667-7206A>G		intron	N/A	ENSP00000501020.1

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

African (AFR) AF: 0.381 AC: 15814 AN: 41480

American (AMR) AF: 0.189 AC: 2893 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3468

East Asian (EAS) AF: 0.0867 AC: 449 AN: 5176

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4824

European-Finnish (FIN) AF: 0.150 AC: 1584 AN: 10594

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13187 AN: 67992

Other (OTH) AF: 0.256 AC: 541 AN: 2114

Alfa AF: 0.204 Hom.: 5656

Bravo AF: 0.243

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.2
DANN	Benign	0.40
PhyloP100		-0.61
PromoterAI		0.024	Neutral

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

Other links and lift over

dbSNP: rs7281019; hg19: chr21-33958347;