rs554776242

Variant names:

• chr12-6328935-AAAAACAAAAC-A
• rs554776242
• NM_001065.4:c.*367_*376delGTTTTGTTTT

Your query was ambiguous. Multiple possible variants found:

• chr12-6328935-AAAAACAAAAC-A
• chr12-6328935-AAAAACAAAAC-AAAAAC
• chr12-6328935-AAAAACAAAAC-AAAAACAAAACAAAAC
• chr12-6328935-AAAAACAAAAC-AAAAACAAAACAAAACAAAAC
• chr12-6328935-AAAAACAAAAC-AAAAACAAAACAAAACAAAACAAAAC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001065.4(TNFRSF1A):​c.*367_*376delGTTTTGTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 240,074 control chromosomes in the GnomAD database, including 12 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0031 (9 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (3 hom.)
• Consequence: TNFRSF1A NM_001065.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

Genes affected

TNFRSF1A (HGNC:11916): (TNF receptor superfamily member 1A) This gene encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00312 (475/152334) while in subpopulation AMR AF= 0.0278 (425/15300). AF 95% confidence interval is 0.0256. There are 9 homozygotes in gnomad4. There are 243 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 475 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF1A	NM_001065.4	c.*367_*376delGTTTTGTTTT		3_prime_UTR_variant	Exon 10 of 10	ENST00000162749.7	NP_001056.1
TNFRSF1A	NM_001346091.2	c.*367_*376delGTTTTGTTTT		3_prime_UTR_variant	Exon 9 of 9		NP_001333020.1
TNFRSF1A	NM_001346092.2	c.*367_*376delGTTTTGTTTT		3_prime_UTR_variant	Exon 11 of 11		NP_001333021.1
TNFRSF1A	NR_144351.2	n.1923_1932delGTTTTGTTTT		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF1A	ENST00000162749	c.*367_*376delGTTTTGTTTT		3_prime_UTR_variant	Exon 10 of 10	1	NM_001065.4	ENSP00000162749.2

Frequencies

GnomAD3 genomes AF: 0.00311 AC: 474 AN: 152216 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00137 AC: 120 AN: 87740 Hom.: 3 AF XY: 0.00119 AC XY: 52 AN XY: 43780

Gnomad4 AFR exome AF: 0.00123

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000104

Gnomad4 OTH exome AF: 0.00226

GnomAD4 genome AF: 0.00312 AC: 475 AN: 152334 Hom.: 9 Cov.: 33 AF XY: 0.00326 AC XY: 243 AN XY: 74494

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.0278

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00568

Bravo AF: 0.00597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs554776242; hg19: chr12-6438101;