1-196740093-A-T

Position:

• chr1-196740093-A-T

Variant summary

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

The NM_000186.4(CFH):​c.2783-526A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,918 control chromosomes in the GnomAD database, including 19,279 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 0.48 (19279 hom., cov: 31)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFH	NM_000186.4	c.2783-526A>T		intron_variant		ENST00000367429.9	NP_000177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFH	ENST00000367429.9	c.2783-526A>T		intron_variant		1	NM_000186.4	ENSP00000356399.4
ENSG00000289697	ENST00000696032.1	c.2783-526A>T		intron_variant				ENSP00000512341.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72241 AN: 151800 Hom.: 19258 Cov.: 31

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.476 AC: 72296 AN: 151918 Hom.: 19279 Cov.: 31 AF XY: 0.473 AC XY: 35167 AN XY: 74274

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.471

Alfa AF: 0.358 Hom.: 6061

Bravo AF: 0.500

Asia WGS AF: 0.465 AC: 1617 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	0.61
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs424535; hg19: chr1-196709223;