21-28410531-A-G

Position:

• chr21-28410531-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000657148.1(ENSG00000232855):​n.1645+6544T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 152,192 control chromosomes in the GnomAD database, including 771 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 0.087 (771 hom., cov: 32)
• Consequence: ENST00000657148.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000657148.1	n.1645+6544T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0874 AC: 13285 AN: 152074 Hom.: 768 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0445

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0679

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

GnomAD4 genome AF: 0.0874 AC: 13296 AN: 152192 Hom.: 771 Cov.: 32 AF XY: 0.0877 AC XY: 6528 AN XY: 74406

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0445

Gnomad4 ASJ AF: 0.0326

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.0316

Gnomad4 NFE AF: 0.0647

Gnomad4 OTH AF: 0.0700

Alfa AF: 0.0801 Hom.: 319

Bravo AF: 0.0866

Asia WGS AF: 0.229 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7278456; hg19: chr21-29782852;