rs499807

Positions:

• chr1-196660374-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000186.4(CFH):​c.58+8199A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 152,234 control chromosomes in the GnomAD database, including 1,761 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.088 (1761 hom., cov: 32)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

Genes affected

CFH (HGNC:4883): (complement factor H) This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Oct 2011]

ENSG00000289697 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFH	NM_000186.4	c.58+8199A>G		intron_variant		ENST00000367429.9	NP_000177.2
CFH	NM_001014975.3	c.58+8199A>G		intron_variant			NP_001014975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFH	ENST00000367429.9	c.58+8199A>G		intron_variant		1	NM_000186.4	ENSP00000356399.4
ENSG00000289697	ENST00000696032.1	c.58+8199A>G		intron_variant				ENSP00000512341.1

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 13348 AN: 152116 Hom.: 1755 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0501

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00357

Gnomad OTH AF: 0.0678

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0880 AC: 13391 AN: 152234 Hom.: 1761 Cov.: 32 AF XY: 0.0866 AC XY: 6449 AN XY: 74462

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.0328

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0501

Gnomad4 SAS AF: 0.0737

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.00357

Gnomad4 OTH AF: 0.0690

Alfa AF: 0.0198 Hom.: 187

Bravo AF: 0.0971

Asia WGS AF: 0.0900 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.48

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: rs499807; hg19: chr1-196629504;