Genetic Variant NM_000595.4:c.*838T>C (chr6-31574531-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000595.4(LTA):c.*838T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,164 control chromosomes in the GnomAD database, including 2,988 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 0.20 ( 2988 hom., cov: 30)

Consequence

LTA
NM_000595.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

Publications

808 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:

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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.

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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA	NM_000595.4	MANE Select	c.*838T>C		downstream_gene	N/A	NP_000586.2
	LTA	NM_001159740.2		c.*838T>C		downstream_gene	N/A	NP_001153212.1	Q5STV3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LTA	ENST00000418386.3	TSL:1 MANE Select	c.*838T>C	downstream_gene	N/A	ENSP00000413450.2	P01374
LTA	ENST00000454783.5	TSL:2	c.*838T>C	downstream_gene	N/A	ENSP00000403495.1	P01374
LTA	ENST00000877327.1		c.*838T>C	downstream_gene	N/A	ENSP00000547386.1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29605

AN:

151046

Hom.:

2988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.326

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.236

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

GnomAD4 genome

AF:

0.196

AC:

29631

AN:

151164

Hom.:

2988

Cov.:

AF XY:

0.197

AC XY:

14541

AN XY:

73770

show subpopulations

African (AFR)

AF:

0.162

AC:

6651

AN:

41158

American (AMR)

AF:

0.193

AC:

2935

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

759

AN:

3460

East Asian (EAS)

AF:

0.191

AC:

978

AN:

5122

South Asian (SAS)

AF:

0.324

AC:

1552

AN:

4786

European-Finnish (FIN)

AF:

0.178

AC:

1848

AN:

10382

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14186

AN:

67774

Other (OTH)

AF:

0.236

AC:

495

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1214

2428

3641

4855

6069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.209

Hom.:

13603

Bravo

AF:

0.194

Asia WGS

AF:

0.275

AC:

954

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.6

(source)

DANN

Benign

0.55

PhyloP100

-1.1

Splicing

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

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over