rs11657992

chr17-45843547-C-T

Variant summary

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

The NR_024559.1(MAPT-AS1):n.649G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 152,282 control chromosomes in the GnomAD database, including 199 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 (198 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1 hom.)
• Consequence: MAPT-AS1 NR_024559.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

Genes affected

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPT-AS1	NR_024559.1	n.649G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPT-AS1	ENST00000634876.2	n.603+194G>A		intron_variant, non_coding_transcript_variant		5
MAPT-AS1	ENST00000649665.1	n.1004G>A		non_coding_transcript_exon_variant	3/3
MAPT-AS1	ENST00000653949.1	n.761G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.0448 AC: 6817 AN: 152108 Hom.: 198 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0251

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00872

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.0378

GnomAD4 exome AF: 0.0357 AC: 2 AN: 56 Hom.: 1 AF XY: 0.0455 AC XY: 2 AN XY: 44

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.0448 AC: 6816 AN: 152226 Hom.: 198 Cov.: 32 AF XY: 0.0435 AC XY: 3240 AN XY: 74422

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.0251

Gnomad4 ASJ AF: 0.0539

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00872

Gnomad4 FIN AF: 0.0812

Gnomad4 NFE AF: 0.0688

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0606 Hom.: 175

Bravo AF: 0.0400

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.17
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11657992; hg19: chr17-43920913;