rs1131542

Variant names:

• chr3-172506136-T-A
• rs1131542
• NM_003810.4:c.*356A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-172506136-T-A
• chr3-172506136-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003810.4(TNFSF10):​c.*356A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000749 in 186,908 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000086 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: TNFSF10 NM_003810.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• Publications: 12 publications found

Genes affected

TNFSF10 (HGNC:11925): (TNF superfamily member 10) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. This protein binds to several members of TNF receptor superfamily including TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and possibly also to TNFRSF11B/OPG. The activity of this protein may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and TNFRSF11B/OPG that cannot induce apoptosis. The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003810.4. 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
	TNFSF10	NM_003810.4	MANE Select	c.*356A>T		3_prime_UTR	Exon 5 of 5	NP_003801.1	Q6IBA9
	TNFSF10	NM_001190942.2		c.*748A>T		3_prime_UTR	Exon 3 of 3	NP_001177871.1	P50591-2
	TNFSF10	NR_033994.2		n.1205A>T		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	ENST00000241261.7	TSL:1 MANE Select	c.*356A>T		3_prime_UTR	Exon 5 of 5	ENSP00000241261.2	P50591-1
	TNFSF10	ENST00000420541.6	TSL:1	c.*748A>T		3_prime_UTR	Exon 3 of 3	ENSP00000389931.2	P50591-2
	TNFSF10	ENST00000855870.1		c.*356A>T		3_prime_UTR	Exon 5 of 5	ENSP00000525929.1

Frequencies

GnomAD3 genomes AF: 0.0000856 AC: 13 AN: 151952 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000286 AC: 1 AN: 34956 Hom.: 0 Cov.: 0 AF XY: 0.0000551 AC XY: 1 AN XY: 18162

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 778

American (AMR) AF: 0.00 AC: 0 AN: 2262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 958

East Asian (EAS) AF: 0.00 AC: 0 AN: 1690

South Asian (SAS) AF: 0.00 AC: 0 AN: 2604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 112

European-Non Finnish (NFE) AF: 0.0000431 AC: 1 AN: 23226

Other (OTH) AF: 0.00 AC: 0 AN: 2058

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000856 AC: 13 AN: 151952 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74218

African (AFR) AF: 0.0000484 AC: 2 AN: 41340

American (AMR) AF: 0.000393 AC: 6 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 12853

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.1
DANN	Benign	0.80
PhyloP100		0.29

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: rs1131542; hg19: chr3-172223926;