6-31572536-A-G

Variant names:

• chr6-31572536-A-G
• rs909253
• NM_000595.4:c.-10+90A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 frequency of 0.351 in 590,314 control chromosomes in the GnomAD database, including 37,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.39 (11682 hom., cov: 31)
  • Exomes 𝑓: 0.34 (26251 hom.)
• Consequence: LTA NM_000595.4 intron
• Clinical Significance: risk factor no assertion criteria provided O:2
• Conservation: PhyloP100: -2.15
• Publications: 454 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).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	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
	LOC100287329	NR_149045.1		n.121+47T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA	ENST00000418386.3	TSL:1 MANE Select	c.-10+90A>G		intron	N/A	ENSP00000413450.2
	LTA	ENST00000454783.5	TSL:2	c.-9-198A>G		intron	N/A	ENSP00000403495.1
	LTA	ENST00000471842.1	TSL:2	n.153+90A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58221 AN: 151044 Hom.: 11669 Cov.: 31

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.: 2 AF XY: 0.335 AC XY: 77185 AN XY: 230318

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

GnomAD4 genome AF: 0.386 AC: 58275 AN: 151164 Hom.: 11682 Cov.: 31 AF XY: 0.382 AC XY: 28191 AN XY: 73772

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: 94 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23028 AN: 67824

Other (OTH) AF: 0.352 AC: 735 AN: 2090

Alfa AF: 0.348 Hom.: 35386

Bravo AF: 0.393

Asia WGS AF: 0.329 AC: 1146 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

Submissions by phenotype

Psoriatic arthritis, susceptibility to Other:1

Feb 15, 2004

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Myocardial infarction, susceptibility to Other:1

Feb 15, 2004

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.16
DANN	Benign	0.68
PhyloP100		-2.2
PromoterAI		-0.023	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs909253; hg19: chr6-31540313;