chr6-31572916-G-C

Variant names:

• chr6-31572916-G-C
• rs3093542
• NM_000595.4:c.100-12G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Publications: 23 publications found

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]

ENSG00000289406 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 232 gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA	NM_000595.4	MANE Select	c.100-12G>C		intron	N/A	NP_000586.2
	LTA	NM_001159740.2		c.100-12G>C		intron	N/A	NP_001153212.1
	LOC100287329	NR_149045.1		n.-213C>G		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA	ENST00000418386.3	TSL:1 MANE Select	c.100-12G>C		intron	N/A	ENSP00000413450.2
	LTA	ENST00000471842.1	TSL:2	n.336G>C		non_coding_transcript_exon	Exon 2 of 3
	LTA	ENST00000489638.5	TSL:5	n.216G>C		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 5984 AN: 151634 Hom.: 232 Cov.: 29

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

GnomAD2 exomes AF: 0.0339 AC: 8349 AN: 246190 AF XY: 0.0333

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 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.: 35 AF XY: 0.0286 AC XY: 20793 AN XY: 726286

African (AFR) AF: 0.0345 AC: 1154 AN: 33472

American (AMR) AF: 0.0128 AC: 573 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00747 AC: 195 AN: 26106

East Asian (EAS) AF: 0.00595 AC: 236 AN: 39694

South Asian (SAS) AF: 0.0104 AC: 894 AN: 86246

European-Finnish (FIN) AF: 0.146 AC: 7576 AN: 52046

Middle Eastern (MID) AF: 0.0331 AC: 191 AN: 5764

European-Non Finnish (NFE) AF: 0.0274 AC: 30429 AN: 1111434

Other (OTH) AF: 0.0242 AC: 1462 AN: 60338

GnomAD4 genome AF: 0.0394 AC: 5986 AN: 151752 Hom.: 232 Cov.: 29 AF XY: 0.0446 AC XY: 3303 AN XY: 74136

African (AFR) AF: 0.0356 AC: 1473 AN: 41372

American (AMR) AF: 0.0226 AC: 345 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00750 AC: 26 AN: 3466

East Asian (EAS) AF: 0.00818 AC: 42 AN: 5132

South Asian (SAS) AF: 0.0129 AC: 62 AN: 4800

European-Finnish (FIN) AF: 0.165 AC: 1740 AN: 10566

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0316 AC: 2143 AN: 67856

Other (OTH) AF: 0.0294 AC: 62 AN: 2106

Alfa AF: 0.0158 Hom.: 8

Bravo AF: 0.0284

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.77
DANN	Benign	0.59
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3093542; hg19: chr6-31540693;