rs2306365

Variant names:

• chr11-65659875-G-A
• rs2306365
• NM_021975.4:c.428-78C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-65659875-G-A
• chr11-65659875-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001404657.1(RELA):​c.461-78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,512,836 control chromosomes in the GnomAD database, including 20,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2691 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17851 hom.)
• Consequence: RELA NM_001404657.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.118
• Publications: 27 publications found

Genes affected

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-65659875-G-A is Benign according to our data. Variant chr11-65659875-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688241.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001404657.1. 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
	RELA	NM_021975.4	MANE Select	c.428-78C>T		intron	N/A	NP_068810.3
	RELA	NM_001404657.1		c.461-78C>T		intron	N/A	NP_001391586.1
	RELA	NM_001145138.2		c.428-87C>T		intron	N/A	NP_001138610.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELA	ENST00000406246.8	TSL:1 MANE Select	c.428-78C>T		intron	N/A	ENSP00000384273.3
	RELA	ENST00000308639.13	TSL:1	c.428-87C>T		intron	N/A	ENSP00000311508.9
	RELA	ENST00000612991.4	TSL:1	c.428-78C>T		intron	N/A	ENSP00000483705.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25723 AN: 152118 Hom.: 2687 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.0900

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.146 AC: 198364 AN: 1360600 Hom.: 17851 Cov.: 26 AF XY: 0.142 AC XY: 95340 AN XY: 669822

African (AFR) AF: 0.210 AC: 6569 AN: 31242

American (AMR) AF: 0.406 AC: 14071 AN: 34694

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 2647 AN: 21546

East Asian (EAS) AF: 0.424 AC: 16373 AN: 38606

South Asian (SAS) AF: 0.0790 AC: 5897 AN: 74646

European-Finnish (FIN) AF: 0.0991 AC: 4196 AN: 42324

Middle Eastern (MID) AF: 0.112 AC: 470 AN: 4178

European-Non Finnish (NFE) AF: 0.132 AC: 139439 AN: 1056896

Other (OTH) AF: 0.154 AC: 8702 AN: 56468

GnomAD4 genome AF: 0.169 AC: 25736 AN: 152236 Hom.: 2691 Cov.: 32 AF XY: 0.170 AC XY: 12648 AN XY: 74448

African (AFR) AF: 0.212 AC: 8791 AN: 41514

American (AMR) AF: 0.295 AC: 4503 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3472

East Asian (EAS) AF: 0.374 AC: 1938 AN: 5178

South Asian (SAS) AF: 0.0876 AC: 423 AN: 4830

European-Finnish (FIN) AF: 0.0900 AC: 956 AN: 10622

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

European-Non Finnish (NFE) AF: 0.121 AC: 8239 AN: 68012

Other (OTH) AF: 0.160 AC: 339 AN: 2114

Alfa AF: 0.113 Hom.: 634

Bravo AF: 0.194

Asia WGS AF: 0.247 AC: 857 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.76
PhyloP100		0.12
PromoterAI		-0.039	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: rs2306365; hg19: chr11-65427346; COSMIC: COSV58014165; COSMIC: COSV58014165;