chr1-196673839-CT-C

Variant names:

• chr1-196673839-CT-C
• rs35507625
• NM_000186.4:c.245-9delT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000186.4(CFH):​c.245-9delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000896 in 1,485,816 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (5 hom., cov: 23)
  • Exomes 𝑓: 0.00055 (4 hom.)
• Consequence: CFH NM_000186.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0950

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 -16 ACMG points.

• BP6: Variant 1-196673839-CT-C is Benign according to our data. Variant chr1-196673839-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1591064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-196673839-CT-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00393 (594/151260) while in subpopulation AFR AF= 0.0138 (569/41248). AF 95% confidence interval is 0.0129. There are 5 homozygotes in gnomad4. There are 286 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFH	NM_000186.4	c.245-9delT		intron_variant	Intron 2 of 21	ENST00000367429.9	NP_000177.2
CFH	NM_001014975.3	c.245-9delT		intron_variant	Intron 2 of 9		NP_001014975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFH	ENST00000367429.9	c.245-9delT		intron_variant	Intron 2 of 21	1	NM_000186.4	ENSP00000356399.4
ENSG00000289697	ENST00000696032.1	c.245-9delT		intron_variant	Intron 2 of 26			ENSP00000512341.1

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 593 AN: 151146 Hom.: 5 Cov.: 23

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000791

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000885

Gnomad OTH AF: 0.00289

GnomAD4 exome AF: 0.000553 AC: 738 AN: 1334556 Hom.: 4 Cov.: 25 AF XY: 0.000489 AC XY: 328 AN XY: 670282

Gnomad4 AFR exome AF: 0.0164

Gnomad4 AMR exome AF: 0.000342

Gnomad4 ASJ exome AF: 0.0000796

Gnomad4 EAS exome AF: 0.0000532

Gnomad4 SAS exome AF: 0.0000967

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.000145

Gnomad4 OTH exome AF: 0.00100

GnomAD4 genome AF: 0.00393 AC: 594 AN: 151260 Hom.: 5 Cov.: 23 AF XY: 0.00387 AC XY: 286 AN XY: 73822

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.000790

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000885

Gnomad4 OTH AF: 0.00286

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Factor H deficiency;C0730295:Basal laminar drusen;C1853147:Age related macular degeneration 4;C2749604:Hemolytic uremic syndrome, atypical, susceptibility to, 1 Benign:1

Jul 28, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Factor H deficiency Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hemolytic uremic syndrome, atypical, susceptibility to, 1 Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Basal laminar drusen Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Age related macular degeneration 4 Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs35507625; hg19: chr1-196642969;