chr21-25316569-A-T

Variant names:

• chr21-25316569-A-T
• rs716195
• ENST00000409758.1:n.89+17168T>A

Variant summary

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

The ENST00000409758.1(ENSG00000222042):​n.89+17168T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,090 control chromosomes in the GnomAD database, including 20,435 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 0.50 (20435 hom., cov: 33)
• Consequence: ENSG00000222042 ENST00000409758.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514
• Publications: 4 publications found

Genes affected

ENSG00000222042 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000222042	ENST00000409758.1	n.89+17168T>A		intron_variant	Intron 1 of 3	3
ENSG00000222042	ENST00000656005.1	n.217+44619T>A		intron_variant	Intron 2 of 4
ENSG00000222042	ENST00000667825.2	n.313+44619T>A		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76058 AN: 151972 Hom.: 20396 Cov.: 33

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.501 AC: 76148 AN: 152090 Hom.: 20435 Cov.: 33 AF XY: 0.499 AC XY: 37064 AN XY: 74344

African (AFR) AF: 0.708 AC: 29359 AN: 41488

American (AMR) AF: 0.509 AC: 7782 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1394 AN: 3472

East Asian (EAS) AF: 0.427 AC: 2212 AN: 5176

South Asian (SAS) AF: 0.446 AC: 2154 AN: 4828

European-Finnish (FIN) AF: 0.393 AC: 4154 AN: 10562

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.408 AC: 27713 AN: 67972

Other (OTH) AF: 0.453 AC: 954 AN: 2108

Alfa AF: 0.459 Hom.: 2086

Bravo AF: 0.518

Asia WGS AF: 0.455 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.41
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs716195; hg19: chr21-26688883;