dbSNP rs2071590: LTA:c.-177-144A>G (chr6-31571991-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 NR_149045.1(LOC100287329):n.121+592T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 154,080 control chromosomes in the GnomAD database, including 36,601 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 0.69 ( 36050 hom., cov: 30)

Exomes 𝑓: 0.69 ( 551 hom. )

Consequence

LOC100287329
NR_149045.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03

Publications

30 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:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_149045.1. 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
	LOC100287329	NR_149045.1		n.121+592T>C		intron	N/A
	LTA	NM_001159740.2		c.-321A>G		upstream_gene	N/A	NP_001153212.1	Q5STV3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289406	ENST00000691266.2		n.199+592T>C		intron	N/A
	LTA	ENST00000454783.5	TSL:2	c.-321A>G		upstream_gene	N/A	ENSP00000403495.1	P01374

Frequencies

GnomAD3 genomes

AF:

0.687

AC:

104168

AN:

151622

Hom.:

36007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.758

Gnomad AMI

AF:

0.707

Gnomad AMR

AF:

0.620

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.768

Gnomad SAS

AF:

0.775

Gnomad FIN

AF:

0.722

Gnomad MID

AF:

0.720

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.687

GnomAD4 exome

AF:

0.688

AC:

1610

AN:

2340

Hom.:

551

AF XY:

0.695

AC XY:

955

AN XY:

1374

show subpopulations

African (AFR)

AF:

0.821

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

0.650

AC:

AN:

European-Finnish (FIN)

AF:

0.710

AC:

1114

AN:

1568

Middle Eastern (MID)

AF:

0.625

AC:

AN:

European-Non Finnish (NFE)

AF:

0.626

AC:

373

AN:

596

Other (OTH)

AF:

0.726

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

103

137

171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.687

AC:

104266

AN:

151740

Hom.:

36050

Cov.:

AF XY:

0.692

AC XY:

51316

AN XY:

74136

show subpopulations

African (AFR)

AF:

0.759

AC:

31382

AN:

41356

American (AMR)

AF:

0.620

AC:

9468

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

2145

AN:

3470

East Asian (EAS)

AF:

0.768

AC:

3946

AN:

5138

South Asian (SAS)

AF:

0.775

AC:

3720

AN:

4798

European-Finnish (FIN)

AF:

0.722

AC:

7620

AN:

10548

Middle Eastern (MID)

AF:

0.712

AC:

208

AN:

292

European-Non Finnish (NFE)

AF:

0.644

AC:

43693

AN:

67866

Other (OTH)

AF:

0.685

AC:

1442

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1686

3373

5059

6746

8432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.637

Hom.:

27893

Bravo

AF:

0.678

Asia WGS

AF:

0.725

AC:

2522

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.5

(source)

DANN

Benign

0.37

PhyloP100

-1.0

PromoterAI

-0.0037

Neutral

(source)

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