chr21-27190227-T-C

Variant names:

• chr21-27190227-T-C
• rs235946
• ENST00000743056.1:n.444-14656T>C

Variant summary

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

The ENST00000743056.1(ENSG00000296857):​n.444-14656T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,966 control chromosomes in the GnomAD database, including 4,363 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 0.23 (4363 hom., cov: 32)
• Consequence: ENSG00000296857 ENST00000743056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 2 publications found

Genes affected

ENSG00000296857 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000743056.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000296857	ENST00000743056.1		n.444-14656T>C		intron	N/A
	ENSG00000296857	ENST00000743057.1		n.463-14656T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34969 AN: 151848 Hom.: 4359 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.230 AC: 34997 AN: 151966 Hom.: 4363 Cov.: 32 AF XY: 0.238 AC XY: 17669 AN XY: 74260

African (AFR) AF: 0.280 AC: 11622 AN: 41470

American (AMR) AF: 0.219 AC: 3346 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3470

East Asian (EAS) AF: 0.481 AC: 2465 AN: 5124

South Asian (SAS) AF: 0.350 AC: 1685 AN: 4816

European-Finnish (FIN) AF: 0.262 AC: 2764 AN: 10536

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11704 AN: 67956

Other (OTH) AF: 0.243 AC: 513 AN: 2112

Alfa AF: 0.204 Hom.: 2491

Bravo AF: 0.229

Asia WGS AF: 0.414 AC: 1439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.55
PhyloP100		-0.040

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs235946;

hg19: chr21-28562546;