rs11582939

chr1-196741027-C-T

Variant summary

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

The NM_000186.4(CFH):c.2956+235C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 518,106 control chromosomes in the GnomAD database, including 10,354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2523 hom., cov: 32)
  • Exomes 𝑓: 0.19 (7831 hom.)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-196741027-C-T is Benign according to our data. Variant chr1-196741027-C-T is described in ClinVar as [Benign]. Clinvar id is 1288303.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFH	NM_000186.4	c.2956+235C>T		intron_variant		ENST00000367429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFH	ENST00000367429.9	c.2956+235C>T		intron_variant		1	NM_000186.4	P2

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24623 AN: 152034 Hom.: 2523 Cov.: 32

Gnomad AFR AF: 0.0894

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.188 AC: 68777 AN: 365954 Hom.: 7831 Cov.: 4 AF XY: 0.185 AC XY: 36123 AN XY: 195756

Gnomad4 AFR exome AF: 0.0896

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.476

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.162 AC: 24623 AN: 152152 Hom.: 2523 Cov.: 32 AF XY: 0.163 AC XY: 12110 AN XY: 74388

Gnomad4 AFR AF: 0.0894

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.163

Alfa AF: 0.172 Hom.: 2256

Bravo AF: 0.172

Asia WGS AF: 0.237 AC: 823 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	10
Dann	Benign	0.58

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: rs11582939; hg19: chr1-196710157;