rs2504172

Positions:

• chrX-147260534-T-C
• chrX-147260534-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NR_030236.1(MIR509-1):​n.92A>G variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 112,006 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. 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 0.00018 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.00014 (0 hom. 17 hem.)
  • Failed GnomAD Quality Control
• Consequence: MIR509-1 NR_030236.1 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

Genes affected

MIR509-1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR509-1	NR_030236.1	n.92A>G		splice_region_variant, non_coding_transcript_exon_variant	1/1
LOC105373347	XR_005647083.2	n.208-8475T>C		intron_variant
LOC105373347	XR_005647084.2	n.158-8475T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR509-1	ENST00000385265.1	n.92A>G		splice_region_variant, non_coding_transcript_exon_variant	1/1	6
ENSG00000284377	ENST00000639829.1	n.412-8475T>C		intron_variant		5
ENSG00000284377	ENST00000701574.1	n.205-8475T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.000179 AC: 20 AN: 111953 Hom.: 0 Cov.: 23 AF XY: 0.0000879 AC XY: 3 AN XY: 34131

Gnomad AFR AF: 0.0000975

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000189

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000565

Gnomad SAS AF: 0.000377

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000226

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000148 AC: 27 AN: 182666 Hom.: 0 AF XY: 0.000103 AC XY: 7 AN XY: 67730

Gnomad AFR exome AF: 0.0000763

Gnomad AMR exome AF: 0.000475

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000362

Gnomad SAS exome AF: 0.000262

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000369

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000139 AC: 38 AN: 273362 Hom.: 0 Cov.: 0 AF XY: 0.000156 AC XY: 17 AN XY: 108774

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000487

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000308

Gnomad4 SAS exome AF: 0.000325

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000431

Gnomad4 OTH exome AF: 0.0000811

GnomAD4 genome AF: 0.000179 AC: 20 AN: 112006 Hom.: 0 Cov.: 23 AF XY: 0.0000877 AC XY: 3 AN XY: 34194

Gnomad4 AFR AF: 0.0000973

Gnomad4 AMR AF: 0.000189

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000567

Gnomad4 SAS AF: 0.000378

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000226

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000868 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2504172; hg19: chrX-146342052; COSMIC: COSV66116265;