chr1-196825389-C-T

Variant names:

• chr1-196825389-C-T
• rs442759
• NM_002113.3:c.59-88C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002113.3(CFHR1):​c.59-88C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,020,500 control chromosomes in the GnomAD database, including 127,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (21414 hom., cov: 23)
  • Exomes 𝑓: 0.43 (105721 hom.)
• Consequence: CFHR1 NM_002113.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.06
• Publications: 3 publications found

Genes affected

CFHR1 (HGNC:4888): (complement factor H related 1) This gene encodes a secreted protein belonging to the complement factor H protein family. It binds to Pseudomonas aeruginosa elongation factor Tuf together with plasminogen, which is proteolytically activated. It is proposed that Tuf acts as a virulence factor by acquiring host proteins to the pathogen surface, controlling complement, and facilitating tissue invasion. Mutations in this gene are associated with an increased risk of atypical hemolytic-uremic syndrome. [provided by RefSeq, Oct 2009]

CFHR1 Gene-Disease associations (from GenCC):

• dense deposit disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hemolytic uremic syndrome, atypical, susceptibility to, 1

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• age related macular degeneration 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 1-196825389-C-T is Benign according to our data. Variant chr1-196825389-C-T is described in ClinVar as Benign. ClinVar VariationId is 1232483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002113.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR1	NM_002113.3	MANE Select	c.59-88C>T		intron	N/A	NP_002104.2	Q03591
	CFHR1	NM_001379306.1		c.59-139C>T		intron	N/A	NP_001366235.1
	CFHR1	NM_001379307.1		c.59-250C>T		intron	N/A	NP_001366236.1	A0A8V8TNS5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFHR1	ENST00000320493.10	TSL:1 MANE Select	c.59-88C>T		intron	N/A	ENSP00000314299.5	Q03591
	CFHR1	ENST00000887404.1		c.59-88C>T		intron	N/A	ENSP00000557463.1
	CFHR1	ENST00000887414.1		c.13-69C>T		intron	N/A	ENSP00000557473.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 63318 AN: 133216 Hom.: 21383 Cov.: 23

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.431 AC: 382349 AN: 887166 Hom.: 105721 Cov.: 12 AF XY: 0.431 AC XY: 192275 AN XY: 446524

African (AFR) AF: 0.592 AC: 8555 AN: 14456

American (AMR) AF: 0.527 AC: 13797 AN: 26194

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 8822 AN: 17340

East Asian (EAS) AF: 0.531 AC: 17569 AN: 33056

South Asian (SAS) AF: 0.421 AC: 21515 AN: 51160

European-Finnish (FIN) AF: 0.390 AC: 16334 AN: 41848

Middle Eastern (MID) AF: 0.401 AC: 1103 AN: 2750

European-Non Finnish (NFE) AF: 0.419 AC: 277385 AN: 661748

Other (OTH) AF: 0.447 AC: 17269 AN: 38614

GnomAD4 genome AF: 0.475 AC: 63385 AN: 133334 Hom.: 21414 Cov.: 23 AF XY: 0.476 AC XY: 30729 AN XY: 64590

African (AFR) AF: 0.589 AC: 18266 AN: 31020

American (AMR) AF: 0.546 AC: 7536 AN: 13808

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1628 AN: 3132

East Asian (EAS) AF: 0.549 AC: 2779 AN: 5064

South Asian (SAS) AF: 0.442 AC: 1711 AN: 3868

European-Finnish (FIN) AF: 0.377 AC: 3652 AN: 9678

Middle Eastern (MID) AF: 0.415 AC: 102 AN: 246

European-Non Finnish (NFE) AF: 0.418 AC: 26641 AN: 63810

Other (OTH) AF: 0.498 AC: 920 AN: 1846

Alfa AF: 0.456 Hom.: 2257

Asia WGS AF: 0.512 AC: 1647 AN: 3220

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.68
DANN	Benign	0.16
PhyloP100		-1.1
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: rs442759; hg19: chr1-196794519;