1-196665976-G-A

Position:

• chr1-196665976-G-A

Variant summary

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

The NM_000186.4(CFH):​c.59-7002G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,070 control chromosomes in the GnomAD database, including 15,059 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 0.40 (15059 hom., cov: 33)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFH	NM_000186.4	c.59-7002G>A		intron_variant		ENST00000367429.9
CFH	NM_001014975.3	c.59-7002G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFH	ENST00000367429.9	c.59-7002G>A		intron_variant		1	NM_000186.4	P2

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59976 AN: 151952 Hom.: 15011 Cov.: 33

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.395 AC: 60091 AN: 152070 Hom.: 15059 Cov.: 33 AF XY: 0.396 AC XY: 29423 AN XY: 74346

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.356

Alfa AF: 0.239 Hom.: 3463

Bravo AF: 0.416

Asia WGS AF: 0.429 AC: 1489 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	1.3
DANN	Benign	0.49

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: rs529825; hg19: chr1-196635106;