6-31952179-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000244255 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELFE	NM_002904.6	c.*122A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000375429.8	NP_002895.3
CFB	NM_001710.6	c.*149T>C		downstream_gene_variant		ENST00000425368.7	NP_001701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELFE	ENST00000375429	c.*122A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_002904.6	ENSP00000364578.3
CFB	ENST00000425368.7	c.*149T>C		downstream_gene_variant		1	NM_001710.6	ENSP00000416561.2
ENSG00000244255	ENST00000456570.5	c.*149T>C		downstream_gene_variant		2		ENSP00000410815.1

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

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0742

Gnomad4 ASJ exome AF: 0.0560

Gnomad4 EAS exome AF: 0.0740

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.0650

Gnomad4 NFE exome AF: 0.0941

Gnomad4 OTH exome AF: 0.108

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

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.0623

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0578

Gnomad4 NFE AF: 0.0911

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0974 Hom.: 634

Bravo AF: 0.124

Asia WGS AF: 0.154 AC: 535 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs760070; hg19: chr6-31919956; COSMIC: COSV105306646; COSMIC: COSV105306646;