chr21-28904780-G-A

Variant names:

• chr21-28904780-G-A
• rs2248610
• ENST00000738660.1:n.159+18G>A

Variant summary

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

The ENST00000738660.1(ENSG00000296381):​n.159+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 146,970 control chromosomes in the GnomAD database, including 4,192 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 0.24 (4192 hom., cov: 27)
• Consequence: ENSG00000296381 ENST00000738660.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 3 publications found

Genes affected

ENSG00000296381 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 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
ENSG00000296381	ENST00000738660.1	n.159+18G>A		intron_variant	Intron 2 of 3
ENSG00000296381	ENST00000738661.1	n.148+18G>A		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 34693 AN: 146868 Hom.: 4182 Cov.: 27

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.298

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.236 AC: 34727 AN: 146970 Hom.: 4192 Cov.: 27 AF XY: 0.236 AC XY: 16854 AN XY: 71288

African (AFR) AF: 0.202 AC: 7991 AN: 39584

American (AMR) AF: 0.218 AC: 3109 AN: 14230

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 758 AN: 3444

East Asian (EAS) AF: 0.105 AC: 504 AN: 4802

South Asian (SAS) AF: 0.264 AC: 1238 AN: 4686

European-Finnish (FIN) AF: 0.266 AC: 2561 AN: 9644

Middle Eastern (MID) AF: 0.294 AC: 83 AN: 282

European-Non Finnish (NFE) AF: 0.264 AC: 17781 AN: 67356

Other (OTH) AF: 0.276 AC: 562 AN: 2034

Alfa AF: 0.247 Hom.: 18276

Bravo AF: 0.220

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.038
DANN	Benign	0.52
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs2248610; hg19: chr21-30277102;