21-34363867-G-A

Position:

• chr21-34363867-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NR_188571.1(LOC105372791):​n.852+6568C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,102 control chromosomes in the GnomAD database, including 22,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.52 (22151 hom., cov: 33)
• Consequence: LOC105372791 NR_188571.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.09

Genes affected

ENSG00000225555 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 21-34363867-G-A is Benign according to our data. Variant chr21-34363867-G-A is described in ClinVar as [Benign]. Clinvar id is 683556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105372791	NR_188571.1	n.852+6568C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000225555	ENST00000440403.2	n.854+6568C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78332 AN: 151984 Hom.: 22155 Cov.: 33

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.515 AC: 78334 AN: 152102 Hom.: 22151 Cov.: 33 AF XY: 0.523 AC XY: 38872 AN XY: 74344

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.542

Alfa AF: 0.591 Hom.: 54048

Bravo AF: 0.506

Asia WGS AF: 0.634 AC: 2209 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13048252; hg19: chr21-35736166;