rs760070

Variant names:

• chr6-31952179-T-C
• rs760070
• NM_002904.6:c.*122A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-31952179-T-C
• chr6-31952179-T-A
• chr6-31952179-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_002904.6(NELFE):​c.*122A>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 0.0992 in 1,433,984 control chromosomes in the GnomAD database, including 7,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1239 hom., cov: 32)
  • Exomes 𝑓: 0.097 (6751 hom.)
• Consequence: NELFE NM_002904.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0240
• Publications: 34 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: AD, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• complement factor b deficiency

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• C3 glomerulonephritis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000244255 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 6-31952179-T-C is Benign according to our data. Variant chr6-31952179-T-C is described in ClinVar as Benign. ClinVar VariationId is 1259467.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002904.6. 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
	NELFE	NM_002904.6	MANE Select	c.*122A>G		3_prime_UTR	Exon 11 of 11	NP_002895.3
	CFB	NM_001710.6	MANE Select	c.*149T>C		downstream_gene	N/A	NP_001701.2	P00751-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELFE	ENST00000375429.8	TSL:1 MANE Select	c.*122A>G		3_prime_UTR	Exon 11 of 11	ENSP00000364578.3	P18615-1
	NELFE	ENST00000948308.1		c.*122A>G		3_prime_UTR	Exon 12 of 12	ENSP00000618367.1
	NELFE	ENST00000882598.1		c.*122A>G		3_prime_UTR	Exon 11 of 11	ENSP00000552657.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17867 AN: 152068 Hom.: 1241 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: 0.0623

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.0971 AC: 124428 AN: 1281798 Hom.: 6751 Cov.: 19 AF XY: 0.0980 AC XY: 62976 AN XY: 642444

African (AFR) AF: 0.190 AC: 5617 AN: 29516

American (AMR) AF: 0.0742 AC: 3049 AN: 41082

Ashkenazi Jewish (ASJ) AF: 0.0560 AC: 1292 AN: 23054

East Asian (EAS) AF: 0.0740 AC: 2871 AN: 38778

South Asian (SAS) AF: 0.149 AC: 11621 AN: 78072

European-Finnish (FIN) AF: 0.0650 AC: 3326 AN: 51158

Middle Eastern (MID) AF: 0.0680 AC: 355 AN: 5222

European-Non Finnish (NFE) AF: 0.0941 AC: 90435 AN: 960814

Other (OTH) AF: 0.108 AC: 5862 AN: 54102

GnomAD4 genome AF: 0.118 AC: 17888 AN: 152186 Hom.: 1239 Cov.: 32 AF XY: 0.115 AC XY: 8584 AN XY: 74422

African (AFR) AF: 0.193 AC: 8017 AN: 41500

American (AMR) AF: 0.102 AC: 1557 AN: 15292

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

East Asian (EAS) AF: 0.0623 AC: 323 AN: 5188

South Asian (SAS) AF: 0.133 AC: 642 AN: 4810

European-Finnish (FIN) AF: 0.0578 AC: 613 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0911 AC: 6192 AN: 68004

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

Alfa AF: 0.100 Hom.: 2450

Bravo AF: 0.124

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		-0.024
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: rs760070; hg19: chr6-31919956; COSMIC: COSV105306646; COSMIC: COSV105306646;