rs2823819

Variant names:

• chr21-16455971-A-G
• rs2823819
• ENST00000400178.7:n.736-31519A>G

Variant summary

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

The ENST00000400178.7(MIR99AHG):​n.736-31519A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,636 control chromosomes in the GnomAD database, including 3,955 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 0.21 (3955 hom., cov: 30)
• Consequence: MIR99AHG ENST00000400178.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 12 publications found

Genes affected

MIR99AHG (HGNC:1274): (mir-99a-let-7c cluster host gene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR99AHG	NR_027790.3	n.470-31519A>G		intron_variant	Intron 4 of 7
MIR99AHG	NR_027791.3	n.388-31519A>G		intron_variant	Intron 3 of 5
MIR99AHG	NR_111004.2	n.515-31519A>G		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR99AHG	ENST00000400178.7	n.736-31519A>G		intron_variant	Intron 5 of 6	3
MIR99AHG	ENST00000413645.2	n.228+64286A>G		intron_variant	Intron 3 of 3	3
MIR99AHG	ENST00000418813.6	n.341-31519A>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32482 AN: 151516 Hom.: 3943 Cov.: 30

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.214 AC: 32514 AN: 151636 Hom.: 3955 Cov.: 30 AF XY: 0.216 AC XY: 15970 AN XY: 74080

African (AFR) AF: 0.325 AC: 13439 AN: 41302

American (AMR) AF: 0.163 AC: 2478 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3464

East Asian (EAS) AF: 0.117 AC: 605 AN: 5162

South Asian (SAS) AF: 0.337 AC: 1603 AN: 4758

European-Finnish (FIN) AF: 0.151 AC: 1599 AN: 10560

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11461 AN: 67892

Other (OTH) AF: 0.207 AC: 435 AN: 2104

Alfa AF: 0.185 Hom.: 8702

Bravo AF: 0.214

Asia WGS AF: 0.209 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		-0.071
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2823819; hg19: chr21-17828291;