rs9977640

Positions:

• chr21-16495968-G-A
• chr21-16495968-G-T

Variant summary

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

The ENST00000445461.7(MIR99AHG):​n.460+8430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 152,166 control chromosomes in the GnomAD database, including 48 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 0.013 (48 hom., cov: 32)
• Consequence: MIR99AHG ENST00000445461.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR99AHG	NR_027790.3	n.518+8430G>A		intron_variant
MIR99AHG	NR_027791.3	n.436+8430G>A		intron_variant
MIR99AHG	NR_111004.2	n.563+8430G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR99AHG	ENST00000400178.7	n.784+8430G>A		intron_variant		3
MIR99AHG	ENST00000413645.2	n.228+104283G>A		intron_variant		3
MIR99AHG	ENST00000418813.6	n.389+8430G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2032 AN: 152048 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.0698

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00861

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

GnomAD4 genome AF: 0.0134 AC: 2037 AN: 152166 Hom.: 48 Cov.: 32 AF XY: 0.0145 AC XY: 1078 AN XY: 74406

Gnomad4 AFR AF: 0.0358

Gnomad4 AMR AF: 0.00380

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.0700

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00303 Hom.: 2

Bravo AF: 0.0127

Asia WGS AF: 0.0510 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.078
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9977640; hg19: chr21-17868288;