rs10922105

Variant names:

• chr1-196721120-A-C
• rs10922105
• NM_000186.4:c.1697-4001A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-196721120-A-C
• chr1-196721120-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000186.4(CFH):​c.1697-4001A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,050 control chromosomes in the GnomAD database, including 14,770 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 0.44 (14770 hom., cov: 31)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.752
• Publications: 6 publications found

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]

CFH Gene-Disease associations (from GenCC):

• primary membranoproliferative glomerulonephritis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• atypical hemolytic-uremic syndrome

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• hemolytic uremic syndrome, atypical, susceptibility to, 1

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• complement factor H deficiency

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• basal laminar drusen

  Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Doyne honeycomb retinal dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dense deposit disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289697 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFH	NM_000186.4	c.1697-4001A>C		intron_variant	Intron 11 of 21	ENST00000367429.9	NP_000177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFH	ENST00000367429.9	c.1697-4001A>C		intron_variant	Intron 11 of 21	1	NM_000186.4	ENSP00000356399.4
ENSG00000289697	ENST00000696032.1	c.1697-4001A>C		intron_variant	Intron 11 of 26			ENSP00000512341.1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66507 AN: 150934 Hom.: 14752 Cov.: 31

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.441 AC: 66562 AN: 151050 Hom.: 14770 Cov.: 31 AF XY: 0.447 AC XY: 32986 AN XY: 73768

African (AFR) AF: 0.466 AC: 19224 AN: 41278

American (AMR) AF: 0.487 AC: 7374 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1807 AN: 3458

East Asian (EAS) AF: 0.449 AC: 2285 AN: 5092

South Asian (SAS) AF: 0.561 AC: 2685 AN: 4788

European-Finnish (FIN) AF: 0.405 AC: 4186 AN: 10334

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27642 AN: 67654

Other (OTH) AF: 0.472 AC: 993 AN: 2104

Alfa AF: 0.272 Hom.: 652

Bravo AF: 0.442

Asia WGS AF: 0.527 AC: 1830 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.6
DANN	Benign	0.60
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10922105; hg19: chr1-196690250;