dbSNP rs6502618: ENSG00000301763:n.67+818A>G (chr17-17843427-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000781607.1(ENSG00000301763):n.67+818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,146 control chromosomes in the GnomAD database, including 23,278 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 0.54 ( 23278 hom., cov: 34)

Exomes 𝑓: 0.70 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000301763
ENST00000781607.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

Publications

6 publications found

Variant links:

Genes affected

ENSG00000301763 (HGNC:):

ENSG00000301763 links:

TOM1L2 (HGNC:11984): (target of myb1 like 2 membrane trafficking protein) This gene belongs to a small gene family whose members have an N-terminal VHS domain followed by a GAT domain; domains which typically participate in vesicular trafficking. The canonical protein encoded by this gene also has a C-terminal clathrin binding motif. This protein has been shown to interact with Tollip, clathrin and ubiquitin and is thought to play a role in endosomal sorting. This gene resides in the 3.7 Mb deletion of chromosome region 17p11.2 that is associated with Smith-Magenis syndrome. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Apr 2017]

TOM1L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOM1L2	NM_001082968.2 link	c.*4208T>C		downstream_gene_variant		ENST00000379504.8	NP_001076437.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ENSG00000301763	ENST00000781607.1 link	n.67+818A>G	intron_variant	Intron 1 of 1
TOM1L2	ENST00000379504.8 link	c.*4208T>C	downstream_gene_variant		2	NM_001082968.2	ENSP00000368818.3
TOM1L2	ENST00000581396.6 link	c.*4208T>C	downstream_gene_variant		1		ENSP00000464297.1

Frequencies

GnomAD3 genomes

AF:

0.539

AC:

81988

AN:

152026

Hom.:

23263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.464

Gnomad ASJ

AF:

0.552

Gnomad EAS

AF:

0.0652

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.562

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.631

Gnomad OTH

AF:

0.536

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.700

AC:

AN:

Hom.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.539

AC:

82052

AN:

152146

Hom.:

23278

Cov.:

AF XY:

0.527

AC XY:

39176

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.500

AC:

20740

AN:

41498

American (AMR)

AF:

0.464

AC:

7091

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.552

AC:

1918

AN:

3472

East Asian (EAS)

AF:

0.0652

AC:

338

AN:

5184

South Asian (SAS)

AF:

0.273

AC:

1315

AN:

4824

European-Finnish (FIN)

AF:

0.562

AC:

5952

AN:

10592

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.631

AC:

42895

AN:

67964

Other (OTH)

AF:

0.536

AC:

1134

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1903

3807

5710

7614

9517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.574

Hom.:

3163

Bravo

AF:

0.531

Asia WGS

AF:

0.247

AC:

864

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.082

(source)

DANN

Benign

0.58

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over