Genetic Variant NM_000595.4:c.100-12G>C (chr6-31572916-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000595.4(LTA):c.100-12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,611,554 control chromosomes in the GnomAD database, including 1,317 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 0.039 ( 232 hom., cov: 29)

Exomes 𝑓: 0.029 ( 1085 hom. )

Consequence

LTA
NM_000595.4 intron

Scores

Splicing: ADA: 0.000007256

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0394 (5986/151752) while in subpopulation AFR AF= 0.0356 (1473/41372). AF 95% confidence interval is 0.0341. There are 232 homozygotes in gnomad4. There are 3303 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 232 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LTA	NM_000595.4 link	c.100-12G>C	intron_variant	Intron 2 of 3	ENST00000418386.3	NP_000586.2	P01374Q5STV3
LTA	NM_001159740.2 link	c.100-12G>C	intron_variant	Intron 2 of 3		NP_001153212.1	P01374Q5STV3
LTA	XM_047418773.1 link	c.100-12G>C	intron_variant	Intron 4 of 5		XP_047274729.1
LOC100287329	NR_149045.1 link	n.-213C>G	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA	ENST00000418386.3 link	c.100-12G>C		intron_variant	Intron 2 of 3	1	NM_000595.4	ENSP00000413450.2		P01374

Frequencies

GnomAD3 genomes

AF:

0.0395

AC:

5984

AN:

151634

Hom.:

232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0357

Gnomad AMI

AF:

0.0912

Gnomad AMR

AF:

0.0227

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.00816

Gnomad SAS

AF:

0.0125

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0316

Gnomad OTH

AF:

0.0302

GnomAD3 exomes

AF:

0.0339

AC:

8349

AN:

246190

Hom.:

339

AF XY:

0.0333

AC XY:

4473

AN XY:

134194

show subpopulations

Gnomad AFR exome

AF:

0.0340

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.00644

Gnomad EAS exome

AF:

0.00438

Gnomad SAS exome

AF:

0.00899

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.0321

Gnomad OTH exome

AF:

0.0328

GnomAD4 exome

AF:

0.0293

AC:

42710

AN:

1459802

Hom.:

1085

Cov.:

AF XY:

0.0286

AC XY:

20793

AN XY:

726286

show subpopulations

Gnomad4 AFR exome

AF:

0.0345

Gnomad4 AMR exome

AF:

0.0128

Gnomad4 ASJ exome

AF:

0.00747

Gnomad4 EAS exome

AF:

0.00595

Gnomad4 SAS exome

AF:

0.0104

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.0274

Gnomad4 OTH exome

AF:

0.0242

GnomAD4 genome

AF:

0.0394

AC:

5986

AN:

151752

Hom.:

232

Cov.:

AF XY:

0.0446

AC XY:

3303

AN XY:

74136

show subpopulations

Gnomad4 AFR

AF:

0.0356

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.00818

Gnomad4 SAS

AF:

0.0129

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.0316

Gnomad4 OTH

AF:

0.0294

Alfa

AF:

0.0158

Hom.:

Bravo

AF:

0.0284

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.77

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000073

dbscSNV1_RF

Benign

0.0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over