rs8904

Variant names:

• chr14-35402011-G-A
• rs8904
• NM_020529.3:c.*2C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-35402011-G-A
• chr14-35402011-G-C
• chr14-35402011-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020529.3(NFKBIA):​c.*2C>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 0.383 in 1,611,958 control chromosomes in the GnomAD database, including 121,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15318 hom., cov: 31)
  • Exomes 𝑓: 0.38 (106090 hom.)
• Consequence: NFKBIA NM_020529.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.295
• Publications: 76 publications found

Genes affected

NFKBIA (HGNC:7797): (NFKB inhibitor alpha) This gene encodes a member of the NF-kappa-B inhibitor family, which contain multiple ankrin repeat domains. The encoded protein interacts with REL dimers to inhibit NF-kappa-B/REL complexes which are involved in inflammatory responses. The encoded protein moves between the cytoplasm and the nucleus via a nuclear localization signal and CRM1-mediated nuclear export. Mutations in this gene have been found in ectodermal dysplasia anhidrotic with T-cell immunodeficiency autosomal dominant disease. [provided by RefSeq, Aug 2011]

NFKBIA Gene-Disease associations (from GenCC):

• ectodermal dysplasia and immunodeficiency 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• ectodermal dysplasia and immune deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 14-35402011-G-A is Benign according to our data. Variant chr14-35402011-G-A is described in ClinVar as Benign. ClinVar VariationId is 313108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020529.3. 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
	NFKBIA	NM_020529.3	MANE Select	c.*2C>T		3_prime_UTR	Exon 6 of 6	NP_065390.1	P25963

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFKBIA	ENST00000216797.10	TSL:1 MANE Select	c.*2C>T		3_prime_UTR	Exon 6 of 6	ENSP00000216797.6	P25963
	NFKBIA	ENST00000860149.1		c.*2C>T		3_prime_UTR	Exon 6 of 6	ENSP00000530208.1
	NFKBIA	ENST00000697961.1		c.*371C>T		3_prime_UTR	Exon 5 of 5	ENSP00000513487.1	A0A8V8TLC3

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66218 AN: 151384 Hom.: 15298 Cov.: 31

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.425

GnomAD2 exomes AF: 0.393 AC: 98581 AN: 251136 AF XY: 0.395

Gnomad AFR exome AF: 0.596

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.418

Gnomad EAS exome AF: 0.421

Gnomad FIN exome AF: 0.401

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.376

GnomAD4 exome AF: 0.377 AC: 550843 AN: 1460456 Hom.: 106090 Cov.: 37 AF XY: 0.378 AC XY: 274984 AN XY: 726578

African (AFR) AF: 0.608 AC: 20338 AN: 33434

American (AMR) AF: 0.293 AC: 13082 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 11038 AN: 26132

East Asian (EAS) AF: 0.359 AC: 14265 AN: 39698

South Asian (SAS) AF: 0.411 AC: 35409 AN: 86218

European-Finnish (FIN) AF: 0.396 AC: 21125 AN: 53410

Middle Eastern (MID) AF: 0.423 AC: 2431 AN: 5744

European-Non Finnish (NFE) AF: 0.369 AC: 409536 AN: 1110762

Other (OTH) AF: 0.391 AC: 23619 AN: 60338

GnomAD4 genome AF: 0.437 AC: 66282 AN: 151502 Hom.: 15318 Cov.: 31 AF XY: 0.435 AC XY: 32217 AN XY: 74008

African (AFR) AF: 0.595 AC: 24561 AN: 41304

American (AMR) AF: 0.336 AC: 5101 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1380 AN: 3464

East Asian (EAS) AF: 0.397 AC: 2041 AN: 5136

South Asian (SAS) AF: 0.433 AC: 2084 AN: 4816

European-Finnish (FIN) AF: 0.402 AC: 4191 AN: 10434

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25688 AN: 67850

Other (OTH) AF: 0.432 AC: 909 AN: 2102

Alfa AF: 0.395 Hom.: 54409

Bravo AF: 0.435

Asia WGS AF: 0.418 AC: 1453 AN: 3478

EpiCase AF: 0.392

EpiControl AF: 0.386

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Ectodermal dysplasia and immunodeficiency 2 (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.27
DANN	Benign	0.84
PhyloP100		-0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs8904; hg19: chr14-35871217; COSMIC: COSV53754079; COSMIC: COSV53754079;