rs2823756

Positions:

• chr21-16370010-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_136541.1(MIR99AHG):​n.523-21604A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,128 control chromosomes in the GnomAD database, including 10,930 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 0.35 (10930 hom., cov: 33)
• Consequence: MIR99AHG NR_136541.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR99AHG	NR_136541.1	n.523-21604A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR99AHG	ENST00000653129.1	n.749-21604A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53767 AN: 152010 Hom.: 10908 Cov.: 33

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.354 AC: 53828 AN: 152128 Hom.: 10930 Cov.: 33 AF XY: 0.352 AC XY: 26152 AN XY: 74364

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.328

Alfa AF: 0.281 Hom.: 8342

Bravo AF: 0.364

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2823756; hg19: chr21-17742330;