6-31952140-T-C

Variant names:

• chr6-31952140-T-C
• rs522162
• NM_002904.6:c.*161A>G

Variant summary

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

The NM_002904.6(NELFE):​c.*161A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 1,507,040 control chromosomes in the GnomAD database, including 8,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1240 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7228 hom.)
• Consequence: NELFE NM_002904.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.114
• Publications: 40 publications found

Genes affected

NELFE (HGNC:13974): (negative elongation factor complex member E) The protein encoded by this gene is part of a complex termed negative elongation factor (NELF) which represses RNA polymerase II transcript elongation. This protein bears similarity to nuclear RNA-binding proteins; however, it has not been demonstrated that this protein binds RNA. The protein contains a tract of alternating basic and acidic residues, largely arginine (R) and aspartic acid (D). The gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. [provided by RefSeq, Jul 2008]

CFB (HGNC:1037): (complement factor B) This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single chain polypeptide. Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. The active subunit Bb is a serine protease which associates with C3b to form the alternative pathway C3 convertase. Bb is involved in the proliferation of preactivated B lymphocytes, while Ba inhibits their proliferation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. This cluster includes several genes involved in regulation of the immune reaction. Polymorphisms in this gene are associated with a reduced risk of age-related macular degeneration. The polyadenylation site of this gene is 421 bp from the 5' end of the gene for complement component 2. [provided by RefSeq, Jul 2008]

CFB Gene-Disease associations (from GenCC):

• atypical hemolytic-uremic syndrome with B factor anomaly

  Inheritance: Unknown, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• complement factor b deficiency

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000244255 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-31952140-T-C is Benign according to our data. Variant chr6-31952140-T-C is described in ClinVar as Benign. ClinVar VariationId is 1227313.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELFE	NM_002904.6	c.*161A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000375429.8	NP_002895.3
CFB	NM_001710.6	c.*110T>C		downstream_gene_variant		ENST00000425368.7	NP_001701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELFE	ENST00000375429.8	c.*161A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_002904.6	ENSP00000364578.3
CFB	ENST00000425368.7	c.*110T>C		downstream_gene_variant		1	NM_001710.6	ENSP00000416561.2
ENSG00000244255	ENST00000456570.5	c.*110T>C		downstream_gene_variant		2		ENSP00000410815.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17861 AN: 152102 Hom.: 1242 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0910

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.0980 AC: 132714 AN: 1354820 Hom.: 7228 Cov.: 21 AF XY: 0.0988 AC XY: 67002 AN XY: 677834

African (AFR) AF: 0.190 AC: 5917 AN: 31172

American (AMR) AF: 0.0743 AC: 3237 AN: 43550

Ashkenazi Jewish (ASJ) AF: 0.0557 AC: 1392 AN: 25000

East Asian (EAS) AF: 0.0740 AC: 2890 AN: 39034

South Asian (SAS) AF: 0.150 AC: 12476 AN: 83444

European-Finnish (FIN) AF: 0.0651 AC: 3181 AN: 48856

Middle Eastern (MID) AF: 0.0681 AC: 364 AN: 5344

European-Non Finnish (NFE) AF: 0.0950 AC: 97060 AN: 1021696

Other (OTH) AF: 0.109 AC: 6197 AN: 56724

GnomAD4 genome AF: 0.117 AC: 17882 AN: 152220 Hom.: 1240 Cov.: 32 AF XY: 0.115 AC XY: 8583 AN XY: 74452

African (AFR) AF: 0.193 AC: 8016 AN: 41514

American (AMR) AF: 0.102 AC: 1555 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3470

East Asian (EAS) AF: 0.0625 AC: 324 AN: 5188

South Asian (SAS) AF: 0.133 AC: 641 AN: 4812

European-Finnish (FIN) AF: 0.0578 AC: 613 AN: 10610

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0910 AC: 6189 AN: 68020

Other (OTH) AF: 0.130 AC: 275 AN: 2114

Alfa AF: 0.103 Hom.: 2481

Bravo AF: 0.124

Asia WGS AF: 0.155 AC: 536 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.9
DANN	Benign	0.72
PhyloP100		0.11
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: rs522162; hg19: chr6-31919917; COSMIC: COSV64887977; COSMIC: COSV64887977;