rs2823615

Positions:

• chr21-16110813-A-T

Variant summary

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

The ENST00000456342.6(MIR99AHG):​n.233+39415A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,950 control chromosomes in the GnomAD database, including 8,271 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 0.32 (8271 hom., cov: 32)
• Consequence: MIR99AHG ENST00000456342.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR99AHG	NR_027790.3	n.312+39415A>T		intron_variant
MIR99AHG	NR_111004.2	n.285+39415A>T		intron_variant
MIR99AHG	NR_111005.2	n.285+39415A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR99AHG	ENST00000400178.7	n.506+39415A>T		intron_variant		3
MIR99AHG	ENST00000456342.6	n.233+39415A>T		intron_variant		2
MIR99AHG	ENST00000602580.6	n.332+39415A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48815 AN: 151832 Hom.: 8253 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.0736

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.322 AC: 48877 AN: 151950 Hom.: 8271 Cov.: 32 AF XY: 0.315 AC XY: 23371 AN XY: 74268

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.0739

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.274

Alfa AF: 0.332 Hom.: 1140

Bravo AF: 0.325

Asia WGS AF: 0.186 AC: 640 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	13
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2823615; hg19: chr21-17483133;