NM_001710.6:c.898-89A>G

Variant names:

• chr6-31948285-A-G
• rs512559
• NM_001710.6:c.898-89A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001710.6(CFB):​c.898-89A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,581,496 control chromosomes in the GnomAD database, including 1,906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.050 (264 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1642 hom.)
• Consequence: CFB NM_001710.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0320

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]

ENSG00000244255 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-31948285-A-G is Benign according to our data. Variant chr6-31948285-A-G is described in ClinVar as [Benign]. Clinvar id is 1279132.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFB	NM_001710.6	c.898-89A>G		intron_variant	Intron 6 of 17	ENST00000425368.7	NP_001701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFB	ENST00000425368.7	c.898-89A>G		intron_variant	Intron 6 of 17	1	NM_001710.6	ENSP00000416561.2
ENSG00000244255	ENST00000456570.5	c.2404-89A>G		intron_variant	Intron 18 of 29	2		ENSP00000410815.1

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7677 AN: 152058 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.0945

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0547

GnomAD4 exome AF: 0.0421 AC: 60215 AN: 1429320 Hom.: 1642 Cov.: 29 AF XY: 0.0401 AC XY: 28568 AN XY: 713034

Gnomad4 AFR exome AF: 0.0931

Gnomad4 AMR exome AF: 0.0383

Gnomad4 ASJ exome AF: 0.0133

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.000447

Gnomad4 FIN exome AF: 0.00494

Gnomad4 NFE exome AF: 0.0483

Gnomad4 OTH exome AF: 0.0416

GnomAD4 genome AF: 0.0505 AC: 7684 AN: 152176 Hom.: 264 Cov.: 32 AF XY: 0.0475 AC XY: 3537 AN XY: 74416

Gnomad4 AFR AF: 0.0944

Gnomad4 AMR AF: 0.0519

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.0404

Gnomad4 OTH AF: 0.0541

Alfa AF: 0.0416 Hom.: 141

Bravo AF: 0.0581

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.4
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs512559; hg19: chr6-31916062;