21-27122121-T-C

Variant names:

• chr21-27122121-T-C
• rs2830713
• ENST00000743056.1:n.346+47288T>C

Variant summary

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

The ENST00000743056.1(ENSG00000296857):​n.346+47288T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,164 control chromosomes in the GnomAD database, including 45,562 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 0.77 (45562 hom., cov: 32)
• Consequence: ENSG00000296857 ENST00000743056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 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.346+47288T>C		intron	N/A
	ENSG00000296857	ENST00000743057.1		n.269+47288T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117236 AN: 152046 Hom.: 45514 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.771 AC: 117343 AN: 152164 Hom.: 45562 Cov.: 32 AF XY: 0.774 AC XY: 57559 AN XY: 74390

African (AFR) AF: 0.850 AC: 35335 AN: 41548

American (AMR) AF: 0.761 AC: 11638 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2536 AN: 3472

East Asian (EAS) AF: 0.818 AC: 4225 AN: 5162

South Asian (SAS) AF: 0.787 AC: 3802 AN: 4828

European-Finnish (FIN) AF: 0.747 AC: 7908 AN: 10580

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49238 AN: 67970

Other (OTH) AF: 0.771 AC: 1629 AN: 2112

Alfa AF: 0.744 Hom.: 130935

Bravo AF: 0.780

Asia WGS AF: 0.812 AC: 2818 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.67
PhyloP100		-1.0

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: rs2830713;

hg19: chr21-28494440;