21-16295399-T-C

Variant names:

• chr21-16295399-T-C
• rs2823743
• ENST00000400178.7:n.663+64284T>C

Variant summary

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

The ENST00000400178.7(MIR99AHG):​n.663+64284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,096 control chromosomes in the GnomAD database, including 7,139 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 0.26 (7139 hom., cov: 32)
• Consequence: MIR99AHG ENST00000400178.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 7 publications found

Genes affected

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

ENSG00000270071 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR99AHG	NR_027790.3	n.469+64284T>C		intron_variant	Intron 4 of 7
MIR99AHG	NR_027791.3	n.315+64284T>C		intron_variant	Intron 2 of 5
MIR99AHG	NR_111004.2	n.442+64284T>C		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR99AHG	ENST00000400178.7	n.663+64284T>C		intron_variant	Intron 4 of 6	3
MIR99AHG	ENST00000413645.2	n.156+64284T>C		intron_variant	Intron 2 of 3	3
MIR99AHG	ENST00000419952.6	n.315+64284T>C		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39421 AN: 151978 Hom.: 7113 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.260 AC: 39498 AN: 152096 Hom.: 7139 Cov.: 32 AF XY: 0.259 AC XY: 19277 AN XY: 74376

African (AFR) AF: 0.490 AC: 20328 AN: 41444

American (AMR) AF: 0.291 AC: 4444 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3464

East Asian (EAS) AF: 0.475 AC: 2450 AN: 5162

South Asian (SAS) AF: 0.177 AC: 855 AN: 4820

European-Finnish (FIN) AF: 0.0817 AC: 867 AN: 10610

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9534 AN: 67998

Other (OTH) AF: 0.238 AC: 502 AN: 2108

Alfa AF: 0.187 Hom.: 11373

Bravo AF: 0.288

Asia WGS AF: 0.283 AC: 984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.65
PhyloP100		-0.071

Splicing

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

Other links and lift over

dbSNP: rs2823743; hg19: chr21-17667720;