21-24046613-G-C

Variant names:

• chr21-24046613-G-C
• rs2828759
• ENST00000434859.1:n.81-2907G>C

Variant summary

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

The ENST00000434859.1(ENSG00000226996):​n.81-2907G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,766 control chromosomes in the GnomAD database, including 33,386 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 0.66 (33386 hom., cov: 30)
• Consequence: ENSG00000226996 ENST00000434859.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297
• Publications: 4 publications found

Genes affected

ENSG00000226996 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000434859.1. 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
	ENSG00000226996	ENST00000434859.1	TSL:3	n.81-2907G>C		intron	N/A
	ENSG00000287801	ENST00000668921.1		n.138-61607C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100444 AN: 151648 Hom.: 33349 Cov.: 30

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.662 AC: 100533 AN: 151766 Hom.: 33386 Cov.: 30 AF XY: 0.663 AC XY: 49142 AN XY: 74164

African (AFR) AF: 0.612 AC: 25319 AN: 41356

American (AMR) AF: 0.680 AC: 10369 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1947 AN: 3472

East Asian (EAS) AF: 0.646 AC: 3313 AN: 5128

South Asian (SAS) AF: 0.690 AC: 3306 AN: 4788

European-Finnish (FIN) AF: 0.673 AC: 7097 AN: 10548

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.692 AC: 46974 AN: 67904

Other (OTH) AF: 0.646 AC: 1366 AN: 2114

Alfa AF: 0.662 Hom.: 3941

Bravo AF: 0.657

Asia WGS AF: 0.666 AC: 2308 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.87
DANN	Benign	0.52
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs2828759; hg19: chr21-25418928;