rs7101916

Variant names:

• chr11-65663889-C-T
• rs7101916
• ENST00000654031.2:n.619C>T

Variant summary

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

The ENST00000654031.2(RELA-DT):​n.619C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,180 control chromosomes in the GnomAD database, including 2,672 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 0.17 (2672 hom., cov: 31)
• Consequence: RELA-DT ENST00000654031.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 25 publications found

Genes affected

RELA-DT (HGNC:54185): (RELA divergent transcript)

RELA (HGNC:9955): (RELA proto-oncogene, NF-kB subunit) NF-kappa-B is a ubiquitous transcription factor involved in several biological processes. It is held in the cytoplasm in an inactive state by specific inhibitors. Upon degradation of the inhibitor, NF-kappa-B moves to the nucleus and activates transcription of specific genes. NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB. The most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene, RELA. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

RELA Gene-Disease associations (from GenCC):

• combined immunodeficiency due to RELA haploinsufficiency

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• mucocutaneous ulceration, chronic

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary pediatric Behçet-like disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELA-DT	NR_183625.1	n.143+741C>T		intron_variant	Intron 1 of 3
RELA	NM_001404662.1	c.-806G>A		upstream_gene_variant			NP_001391591.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELA-DT	ENST00000654031.2	n.619C>T		non_coding_transcript_exon_variant	Exon 2 of 4
RELA-DT	ENST00000685480.3	n.889C>T		non_coding_transcript_exon_variant	Exon 1 of 1
RELA-DT	ENST00000820202.1	n.54C>T		non_coding_transcript_exon_variant	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25587 AN: 152062 Hom.: 2666 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.0937

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.168 AC: 25610 AN: 152180 Hom.: 2672 Cov.: 31 AF XY: 0.169 AC XY: 12599 AN XY: 74416

African (AFR) AF: 0.207 AC: 8583 AN: 41492

American (AMR) AF: 0.295 AC: 4515 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3470

East Asian (EAS) AF: 0.381 AC: 1970 AN: 5170

South Asian (SAS) AF: 0.0942 AC: 454 AN: 4820

European-Finnish (FIN) AF: 0.0898 AC: 953 AN: 10616

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8250 AN: 68002

Other (OTH) AF: 0.160 AC: 338 AN: 2110

Alfa AF: 0.146 Hom.: 4688

Bravo AF: 0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.68
PhyloP100		-0.060

Splicing

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

Other links and lift over

dbSNP: rs7101916; hg19: chr11-65431360;