ENST00000649665.1:n.1004G>A

Variant names:

• chr17-45843547-C-T
• rs11657992
• ENST00000649665.1:n.1004G>A

Variant summary

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

The ENST00000649665.1(MAPT-AS1):​n.1004G>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 ENST00000649665.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MAPT-AS1	NR_024559.1	n.649G>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPT-AS1	ENST00000649665.1	n.1004G>A		non_coding_transcript_exon_variant	Exon 3 of 3
MAPT-AS1	ENST00000653949.2	n.840G>A		non_coding_transcript_exon_variant	Exon 2 of 2
MAPT-AS1	ENST00000634876.2	n.603+194G>A		intron_variant	Intron 2 of 6	5
MAPT-AS1	ENST00000579244.1	n.*104G>A		downstream_gene_variant		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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 34

Other (OTH) AF: 0.250 AC: 2 AN: 8

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

African (AFR) AF: 0.0134 AC: 558 AN: 41544

American (AMR) AF: 0.0251 AC: 384 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00872 AC: 42 AN: 4814

European-Finnish (FIN) AF: 0.0812 AC: 860 AN: 10596

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0688 AC: 4677 AN: 68006

Other (OTH) AF: 0.0374 AC: 79 AN: 2114

Alfa AF: 0.0574 Hom.: 283

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
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs11657992; hg19: chr17-43920913;