21-45613991-C-A

Position:

• chr21-45613991-C-A

Variant summary

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

The ENST00000651182.1(ENSG00000286082):​n.382+1608G>T 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 0.0951 in 152,128 control chromosomes in the GnomAD database, including 759 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 0.095 (759 hom., cov: 31)
• Consequence: ENST00000651182.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

Genes affected

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC107985485	XR_001755092.2	n.199+1608G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000651182.1	n.382+1608G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0951 AC: 14457 AN: 152010 Hom.: 758 Cov.: 31

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.0855

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0958

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

GnomAD4 genome AF: 0.0951 AC: 14465 AN: 152128 Hom.: 759 Cov.: 31 AF XY: 0.0933 AC XY: 6939 AN XY: 74372

Gnomad4 AFR AF: 0.0695

Gnomad4 AMR AF: 0.0741

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0216

Gnomad4 SAS AF: 0.0630

Gnomad4 FIN AF: 0.0855

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.0948

Alfa AF: 0.0959 Hom.: 406

Bravo AF: 0.0923

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9980967; hg19: chr21-47033905;