chr22-19014231-G-A

Variant names:

• chr22-19014231-G-A
• rs10483098
• ENST00000440005.6:n.685-122G>A

Variant summary

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

The ENST00000440005.6(DGCR5):​n.685-122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 699,296 control chromosomes in the GnomAD database, including 93 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 0.018 (68 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (25 hom.)
• Consequence: DGCR5 ENST00000440005.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 0 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]

ENSG00000283366 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0585 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR5	NR_024159.2		n.598-122G>A		intron	N/A
	DGCR5	NR_026651.2		n.598-122G>A		intron	N/A
	DGCR5	NR_110533.2		n.742-122G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR5	ENST00000440005.6	TSL:1	n.685-122G>A		intron	N/A
	DGCR5	ENST00000424407.2	TSL:2	n.480-122G>A		intron	N/A
	DGCR5	ENST00000609630.2	TSL:6	n.619-122G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2705 AN: 151788 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00735

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.00261 AC: 1429 AN: 547414 Hom.: 25 AF XY: 0.00223 AC XY: 657 AN XY: 294160

African (AFR) AF: 0.0579 AC: 865 AN: 14934

American (AMR) AF: 0.00355 AC: 113 AN: 31824

Ashkenazi Jewish (ASJ) AF: 0.00896 AC: 159 AN: 17752

East Asian (EAS) AF: 0.0000668 AC: 2 AN: 29942

South Asian (SAS) AF: 0.000155 AC: 9 AN: 58106

European-Finnish (FIN) AF: 0.000333 AC: 15 AN: 45018

Middle Eastern (MID) AF: 0.00179 AC: 4 AN: 2232

European-Non Finnish (NFE) AF: 0.000411 AC: 131 AN: 318916

Other (OTH) AF: 0.00457 AC: 131 AN: 28690

GnomAD4 genome AF: 0.0179 AC: 2713 AN: 151882 Hom.: 68 Cov.: 32 AF XY: 0.0177 AC XY: 1315 AN XY: 74202

African (AFR) AF: 0.0604 AC: 2502 AN: 41390

American (AMR) AF: 0.00735 AC: 112 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 67968

Other (OTH) AF: 0.0162 AC: 34 AN: 2102

Alfa AF: 0.00657 Hom.: 23

Bravo AF: 0.0205

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.8
DANN	Benign	0.58
PhyloP100		0.053

Splicing

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

Other links and lift over

dbSNP: rs10483098; hg19: chr22-19001744;