22-18979346-G-A

Variant names:

• chr22-18979346-G-A
• rs2078743
• ENST00000440005.6:n.135-8411G>A

Variant summary

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

The ENST00000440005.6(DGCR5):​n.135-8411G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 151,850 control chromosomes in the GnomAD database, including 888 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 0.098 (888 hom., cov: 30)
• Consequence: DGCR5 ENST00000440005.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• Publications: 14 publications found

Genes affected

DGCR5 (HGNC:16757): (DiGeorge syndrome critical region gene 5) Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000440005.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR5	NR_002733.3		n.192-8411G>A		intron	N/A
	DGCR5	NR_024159.2		n.191+8688G>A		intron	N/A
	DGCR5	NR_026651.2		n.191+8688G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR5	ENST00000440005.6	TSL:1	n.135-8411G>A		intron	N/A
	DGCR5	ENST00000421572.2	TSL:2	n.145-6490G>A		intron	N/A
	DGCR5	ENST00000438934.5	TSL:5	n.146-8411G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 14912 AN: 151732 Hom.: 884 Cov.: 30

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0669

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0154

Gnomad FIN AF: 0.0416

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.0961

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

GnomAD4 genome AF: 0.0983 AC: 14928 AN: 151850 Hom.: 888 Cov.: 30 AF XY: 0.0941 AC XY: 6988 AN XY: 74222

African (AFR) AF: 0.163 AC: 6725 AN: 41364

American (AMR) AF: 0.0668 AC: 1018 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3468

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5160

South Asian (SAS) AF: 0.0154 AC: 74 AN: 4790

European-Finnish (FIN) AF: 0.0416 AC: 440 AN: 10568

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0905 AC: 6152 AN: 67944

Other (OTH) AF: 0.0946 AC: 199 AN: 2104

Alfa AF: 0.0893 Hom.: 701

Bravo AF: 0.104

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs2078743; hg19: chr22-18966859;