rs12038333

Positions:

• chr1-196703324-G-A
• chr1-196703324-G-T

Variant summary

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

The NM_000186.4(CFH):​c.1337-10411G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,008 control chromosomes in the GnomAD database, including 32,329 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 0.65 (32329 hom., cov: 32)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFH	NM_000186.4	c.1337-10411G>A		intron_variant		ENST00000367429.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFH	ENST00000367429.9	c.1337-10411G>A		intron_variant		1	NM_000186.4	P2

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98354 AN: 151890 Hom.: 32306 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.647 AC: 98420 AN: 152008 Hom.: 32329 Cov.: 32 AF XY: 0.651 AC XY: 48352 AN XY: 74302

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.666

Alfa AF: 0.550 Hom.: 13323

Bravo AF: 0.664

Asia WGS AF: 0.781 AC: 2716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.98
DANN	Benign	0.26

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: rs12038333; hg19: chr1-196672454;