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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000781607.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TOM1L2	NM_001082968.2	MANE Select	c.*4208T>C	downstream_gene	N/A	NP_001076437.1	Q6ZVM7-1
TOM1L2	NM_001350332.2		c.*4208T>C	downstream_gene	N/A	NP_001337261.1
TOM1L2	NM_001350333.2		c.*4208T>C	downstream_gene	N/A	NP_001337262.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENSG00000301763	ENST00000781607.1		n.67+818A>G	intron	N/A
TOM1L2	ENST00000379504.8	TSL:2 MANE Select	c.*4208T>C	downstream_gene	N/A	ENSP00000368818.3	Q6ZVM7-1
TOM1L2	ENST00000581396.6	TSL:1	c.*4208T>C	downstream_gene	N/A	ENSP00000464297.1	Q6ZVM7-2

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over