rs2018708

Variant names:

• chr21-16600710-A-G
• rs2018708
• ENST00000400178.7:n.785-6284A>G

Variant summary

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

The ENST00000400178.7(MIR99AHG):​n.785-6284A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 152,172 control chromosomes in the GnomAD database, including 315 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 0.045 (315 hom., cov: 32)
• Consequence: MIR99AHG ENST00000400178.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR99AHG	NR_027790.3	n.694+6256A>G		intron_variant	Intron 7 of 7
MIR99AHG	NR_027791.3	n.498-6284A>G		intron_variant	Intron 5 of 5
MIR99AHG	NR_111004.2	n.564-6284A>G		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR99AHG	ENST00000400178.7	n.785-6284A>G		intron_variant	Intron 6 of 6	3
MIR99AHG	ENST00000413645.2	n.229-39520A>G		intron_variant	Intron 3 of 3	3
MIR99AHG	ENST00000418813.6	n.451-6284A>G		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0445 AC: 6762 AN: 152052 Hom.: 310 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.0387

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

GnomAD4 genome AF: 0.0446 AC: 6782 AN: 152172 Hom.: 315 Cov.: 32 AF XY: 0.0441 AC XY: 3283 AN XY: 74398

African (AFR) AF: 0.118 AC: 4878 AN: 41460

American (AMR) AF: 0.0296 AC: 453 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3472

East Asian (EAS) AF: 0.0506 AC: 262 AN: 5178

South Asian (SAS) AF: 0.0245 AC: 118 AN: 4826

European-Finnish (FIN) AF: 0.00264 AC: 28 AN: 10606

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0132 AC: 896 AN: 68026

Other (OTH) AF: 0.0383 AC: 81 AN: 2116

Alfa AF: 0.0241 Hom.: 179

Bravo AF: 0.0505

Asia WGS AF: 0.0490 AC: 171 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.49
PhyloP100		-0.031
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: rs2018708; hg19: chr21-17973030;