rs909253

Variant names:

Your query was ambiguous. Multiple possible variants found:

Germline classification Cancer classification (beta)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BA1BP4_Strong

The NM_000595.4(LTA):c.-10+90A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.351 (AC=207,302) in the gnomAD database across 590,314 control chromosomes, including 37,933 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.503. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (no review stars).

Frequency

Genomes: 𝑓 0.39 ( 11682 hom., cov: 31)

Exomes 𝑓: 0.34 ( 26251 hom. )

Consequence

LTA
NM_000595.4 intron

Scores

Clinical Significance

risk factor no assertion criteria provided O:2

Conservation

PhyloP100: -2.15

Publications

457 publications found

Variant links:

Genes affected

LTA (HGNC:6709): (lymphotoxin alpha) The encoded protein, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The protein is highly inducible, secreted, and forms heterotrimers with lymphotoxin-beta which anchor lymphotoxin-alpha to the cell surface. This protein also mediates a large variety of inflammatory, immunostimulatory, and antiviral responses, is involved in the formation of secondary lymphoid organs during development and plays a role in apoptosis. Genetic variations in this gene are associated with susceptibility to leprosy type 4, myocardial infarction, non-Hodgkin's lymphoma, and psoriatic arthritis. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

LTA links:

ENSG00000289406 (HGNC:):

ENSG00000289406 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000595.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.5033 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000595.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LTA	NM_000595.4	MANE Select	c.-10+90A>G	intron	N/A	NP_000586.2
LTA	NM_001159740.2		c.-9-198A>G	intron	N/A	NP_001153212.1	Q5STV3
LOC100287329	NR_149045.1		n.121+47T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LTA	ENST00000418386.3	TSL:1 MANE Select	c.-10+90A>G	intron	N/A	ENSP00000413450.2	P01374
LTA	ENST00000877327.1		c.-207A>G	5_prime_UTR	Exon 1 of 3	ENSP00000547386.1
LTA	ENST00000454783.5	TSL:2	c.-9-198A>G	intron	N/A	ENSP00000403495.1	P01374

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58221

AN:

151044

Hom.:

11669

Cov.:

show subpopulations

Gnomad AFR

AF:

0.509

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.279

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.354

GnomAD4 exome

AF:

0.339

AC:

149027

AN:

439150

Hom.:

26251

Cov.:

AF XY:

0.335

AC XY:

77185

AN XY:

230318

show subpopulations

African (AFR)

AF:

0.505

AC:

6190

AN:

12254

American (AMR)

AF:

0.332

AC:

6015

AN:

18132

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

3425

AN:

13510

East Asian (EAS)

AF:

0.421

AC:

12933

AN:

30688

South Asian (SAS)

AF:

0.283

AC:

12037

AN:

42514

European-Finnish (FIN)

AF:

0.321

AC:

9523

AN:

29700

Middle Eastern (MID)

AF:

0.335

AC:

763

AN:

2278

European-Non Finnish (NFE)

AF:

0.337

AC:

89228

AN:

264386

Other (OTH)

AF:

0.347

AC:

8913

AN:

25688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

4986

9972

14957

19943

24929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.386

AC:

58275

AN:

151164

Hom.:

11682

Cov.:

AF XY:

0.382

AC XY:

28191

AN XY:

73772

show subpopulations

African (AFR)

AF:

0.509

AC:

20963

AN:

41182

American (AMR)

AF:

0.350

AC:

5311

AN:

15166

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

835

AN:

3460

East Asian (EAS)

AF:

0.477

AC:

2441

AN:

5114

South Asian (SAS)

AF:

0.280

AC:

1344

AN:

4806

European-Finnish (FIN)

AF:

0.309

AC:

3189

AN:

10320

Middle Eastern (MID)

AF:

0.322

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.340

AC:

23028

AN:

67824

Other (OTH)

AF:

0.352

AC:

735

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1821

3641

5462

7282

9103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.348

Hom.:

35386

Bravo

AF:

0.393

Asia WGS

AF:

0.329

AC:

1146

AN:

3478

Local populations

Turkish Variome

AF:

0.269

AC:

416

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.518

AC:

4644

AN:

8960

Hom.:

1227

ABraOM SABE-WGS-1171

AF:

0.332

AC:

778

AN:

2342

Hom.:

138

ClinVar

ClinVar submissions

Significance:risk factor

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Myocardial infarction, susceptibility to (1)

Psoriatic arthritis, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.16

(source)

DANN

Benign

0.68

PhyloP100

-2.2

PromoterAI

-0.023

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over