ENST00000454622.2:n.201+35035G>A

Variant names:

• chr21-33035869-C-T
• rs762237
• ENST00000454622.2:n.201+35035G>A

Variant summary

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

The ENST00000454622.2(ENSG00000227757):​n.201+35035G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 145,384 control chromosomes in the GnomAD database, including 6,861 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 0.30 (6861 hom., cov: 27)
• Consequence: ENSG00000227757 ENST00000454622.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 10 publications found

Genes affected

ENSG00000227757 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.357 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
ENSG00000227757	ENST00000454622.2	n.201+35035G>A		intron_variant	Intron 1 of 1	2
ENSG00000227757	ENST00000777421.1	n.91+35035G>A		intron_variant	Intron 1 of 1
ENSG00000227757	ENST00000777422.1	n.108-12943G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 42969 AN: 145326 Hom.: 6859 Cov.: 27

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.296 AC: 42995 AN: 145384 Hom.: 6861 Cov.: 27 AF XY: 0.297 AC XY: 20969 AN XY: 70520

African (AFR) AF: 0.179 AC: 6835 AN: 38154

American (AMR) AF: 0.282 AC: 4069 AN: 14444

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1203 AN: 3446

East Asian (EAS) AF: 0.197 AC: 963 AN: 4876

South Asian (SAS) AF: 0.372 AC: 1740 AN: 4678

European-Finnish (FIN) AF: 0.369 AC: 3389 AN: 9192

Middle Eastern (MID) AF: 0.284 AC: 79 AN: 278

European-Non Finnish (NFE) AF: 0.350 AC: 23576 AN: 67396

Other (OTH) AF: 0.306 AC: 621 AN: 2028

Alfa AF: 0.322 Hom.: 10492

Bravo AF: 0.273

Asia WGS AF: 0.320 AC: 1113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.75
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs762237; hg19: chr21-34408177;