chr17-45874351-G-A

Variant names:

• chr17-45874351-G-A
• rs2055794
• ENST00000579599.1:n.902+20261C>T

Variant summary

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

The ENST00000579599.1(MAPT-AS1):​n.902+20261C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,910 control chromosomes in the GnomAD database, including 2,139 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 0.14 (2139 hom., cov: 32)
• Consequence: MAPT-AS1 ENST00000579599.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• Publications: 22 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPT-AS1	NR_024559.1	n.34+21129C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPT-AS1	ENST00000579599.1	n.902+20261C>T		intron_variant	Intron 1 of 1	1
MAPT-AS1	ENST00000579244.1	n.121+21129C>T		intron_variant	Intron 1 of 1	2
MAPT-AS1	ENST00000634876.2	n.182+21129C>T		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21842 AN: 151794 Hom.: 2141 Cov.: 32

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.144 AC: 21832 AN: 151910 Hom.: 2139 Cov.: 32 AF XY: 0.135 AC XY: 9994 AN XY: 74218

African (AFR) AF: 0.0431 AC: 1787 AN: 41428

American (AMR) AF: 0.176 AC: 2688 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.0741 AC: 356 AN: 4802

European-Finnish (FIN) AF: 0.0658 AC: 690 AN: 10480

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14767 AN: 67956

Other (OTH) AF: 0.182 AC: 383 AN: 2106

Alfa AF: 0.185 Hom.: 1624

Bravo AF: 0.148

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.52
PhyloP100		-0.96

Splicing

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

Other links and lift over

dbSNP: rs2055794; hg19: chr17-43951717;