rs696

Variant names:

• chr14-35401887-C-T
• rs696
• NM_020529.3:c.*126G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-35401887-C-T
• chr14-35401887-C-A
• chr14-35401887-C-G

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.*126G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,053,372 control chromosomes in the GnomAD database, including 77,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15857 hom., cov: 33)
  • Exomes 𝑓: 0.36 (61343 hom.)
• Consequence: NFKBIA NM_020529.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.184
• Publications: 147 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=-0.71).
• BP6: Variant 14-35401887-C-T is Benign according to our data. Variant chr14-35401887-C-T is described in ClinVar as Benign. ClinVar VariationId is 313105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 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.*126G>A		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.*126G>A		3_prime_UTR	Exon 6 of 6	ENSP00000216797.6	P25963
	NFKBIA	ENST00000860149.1		c.*126G>A		3_prime_UTR	Exon 6 of 6	ENSP00000530208.1
	NFKBIA	ENST00000697961.1		c.*495G>A		3_prime_UTR	Exon 5 of 5	ENSP00000513487.1	A0A8V8TLC3

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67180 AN: 151942 Hom.: 15835 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.362 AC: 326365 AN: 901312 Hom.: 61343 Cov.: 12 AF XY: 0.366 AC XY: 170900 AN XY: 467516

African (AFR) AF: 0.602 AC: 11938 AN: 19834

American (AMR) AF: 0.293 AC: 11186 AN: 38114

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 9240 AN: 22064

East Asian (EAS) AF: 0.352 AC: 11894 AN: 33748

South Asian (SAS) AF: 0.403 AC: 27749 AN: 68908

European-Finnish (FIN) AF: 0.395 AC: 19391 AN: 49104

Middle Eastern (MID) AF: 0.396 AC: 1175 AN: 2968

European-Non Finnish (NFE) AF: 0.349 AC: 218167 AN: 625302

Other (OTH) AF: 0.379 AC: 15625 AN: 41270

GnomAD4 genome AF: 0.442 AC: 67247 AN: 152060 Hom.: 15857 Cov.: 33 AF XY: 0.439 AC XY: 32650 AN XY: 74298

African (AFR) AF: 0.611 AC: 25323 AN: 41464

American (AMR) AF: 0.337 AC: 5157 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1388 AN: 3472

East Asian (EAS) AF: 0.398 AC: 2060 AN: 5174

South Asian (SAS) AF: 0.433 AC: 2086 AN: 4814

European-Finnish (FIN) AF: 0.399 AC: 4215 AN: 10564

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25768 AN: 67974

Other (OTH) AF: 0.437 AC: 920 AN: 2106

Alfa AF: 0.401 Hom.: 10999

Bravo AF: 0.441

Asia WGS AF: 0.422 AC: 1468 AN: 3478

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)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs696; hg19: chr14-35871093; COSMIC: COSV53754196; COSMIC: COSV53754196;