6-31952053-C-T

Variant names:

• chr6-31952053-C-T
• rs4151672
• NM_001710.6:c.*23C>T

Variant summary

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

The NM_001710.6(CFB):​c.*23C>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 0.0418 in 1,611,310 control chromosomes in the GnomAD database, including 1,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (108 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1421 hom.)
• Consequence: CFB NM_001710.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.172
• Publications: 40 publications found

Genes affected

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]

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]

ENSG00000244255 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-31952053-C-T is Benign according to our data. Variant chr6-31952053-C-T is described in ClinVar as Benign. ClinVar VariationId is 356297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001710.6. 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
	CFB	NM_001710.6	MANE Select	c.*23C>T		3_prime_UTR	Exon 18 of 18	NP_001701.2	P00751-1
	NELFE	NM_002904.6	MANE Select	c.*248G>A		downstream_gene	N/A	NP_002895.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFB	ENST00000425368.7	TSL:1 MANE Select	c.*23C>T		3_prime_UTR	Exon 18 of 18	ENSP00000416561.2	P00751-1
	CFB	ENST00000885733.1		c.*23C>T		3_prime_UTR	Exon 18 of 18	ENSP00000555792.1
	CFB	ENST00000885731.1		c.*23C>T		3_prime_UTR	Exon 18 of 18	ENSP00000555790.1

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5149 AN: 152082 Hom.: 106 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0250

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.0221

Gnomad SAS AF: 0.0558

Gnomad FIN AF: 0.0554

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0458

Gnomad OTH AF: 0.0311

GnomAD2 exomes AF: 0.0386 AC: 9400 AN: 243236 AF XY: 0.0404

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0246

Gnomad EAS exome AF: 0.0180

Gnomad FIN exome AF: 0.0567

Gnomad NFE exome AF: 0.0453

Gnomad OTH exome AF: 0.0371

GnomAD4 exome AF: 0.0426 AC: 62213 AN: 1459110 Hom.: 1421 Cov.: 32 AF XY: 0.0432 AC XY: 31380 AN XY: 725886

African (AFR) AF: 0.0124 AC: 414 AN: 33480

American (AMR) AF: 0.0226 AC: 1011 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 670 AN: 26134

East Asian (EAS) AF: 0.0220 AC: 875 AN: 39700

South Asian (SAS) AF: 0.0516 AC: 4454 AN: 86250

European-Finnish (FIN) AF: 0.0553 AC: 2813 AN: 50856

Middle Eastern (MID) AF: 0.0269 AC: 155 AN: 5760

European-Non Finnish (NFE) AF: 0.0445 AC: 49515 AN: 1111834

Other (OTH) AF: 0.0382 AC: 2306 AN: 60374

GnomAD4 genome AF: 0.0339 AC: 5155 AN: 152200 Hom.: 108 Cov.: 32 AF XY: 0.0347 AC XY: 2586 AN XY: 74432

African (AFR) AF: 0.0123 AC: 509 AN: 41524

American (AMR) AF: 0.0253 AC: 387 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0251 AC: 87 AN: 3472

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5188

South Asian (SAS) AF: 0.0554 AC: 267 AN: 4818

European-Finnish (FIN) AF: 0.0554 AC: 587 AN: 10602

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0459 AC: 3118 AN: 67998

Other (OTH) AF: 0.0308 AC: 65 AN: 2110

Alfa AF: 0.0398 Hom.: 477

Bravo AF: 0.0292

Asia WGS AF: 0.0400 AC: 138 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Atypical hemolytic-uremic syndrome with B factor anomaly (1)
-	-	1	Macular degeneration (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.68
PhyloP100		0.17
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: rs4151672; hg19: chr6-31919830;