1-196827110-T-A

Variant names:

• chr1-196827110-T-A
• rs438781
• NM_002113.3:c.430+105T>A

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.430+105T>A 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 1,175,806 control chromosomes in the GnomAD database, including 148,859 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (22960 hom., cov: 25)
  • Exomes 𝑓: 0.43 (125899 hom.)
• Consequence: CFHR1 NM_002113.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.94
• Publications: 8 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
• age related macular degeneration 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• hemolytic uremic syndrome, atypical, susceptibility to, 1

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 1-196827110-T-A is Benign according to our data. Variant chr1-196827110-T-A is described in ClinVar as Benign. ClinVar VariationId is 1290026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFHR1	NM_002113.3	c.430+105T>A		intron_variant	Intron 3 of 5	ENST00000320493.10	NP_002104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFHR1	ENST00000320493.10	c.430+105T>A		intron_variant	Intron 3 of 5	1	NM_002113.3	ENSP00000314299.5

Frequencies

GnomAD3 genomes AF: 0.493 AC: 66164 AN: 134086 Hom.: 22920 Cov.: 25

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.429 AC: 447273 AN: 1041606 Hom.: 125899 AF XY: 0.429 AC XY: 225450 AN XY: 525726

African (AFR) AF: 0.663 AC: 11823 AN: 17834

American (AMR) AF: 0.531 AC: 19884 AN: 37430

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 10561 AN: 20650

East Asian (EAS) AF: 0.528 AC: 19085 AN: 36154

South Asian (SAS) AF: 0.422 AC: 26759 AN: 63394

European-Finnish (FIN) AF: 0.392 AC: 18373 AN: 46836

Middle Eastern (MID) AF: 0.421 AC: 1657 AN: 3932

European-Non Finnish (NFE) AF: 0.414 AC: 319007 AN: 770484

Other (OTH) AF: 0.448 AC: 20124 AN: 44892

GnomAD4 genome AF: 0.494 AC: 66245 AN: 134200 Hom.: 22960 Cov.: 25 AF XY: 0.494 AC XY: 32263 AN XY: 65248

African (AFR) AF: 0.663 AC: 20713 AN: 31226

American (AMR) AF: 0.553 AC: 7747 AN: 14010

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1649 AN: 3148

East Asian (EAS) AF: 0.549 AC: 2789 AN: 5082

South Asian (SAS) AF: 0.439 AC: 1718 AN: 3914

European-Finnish (FIN) AF: 0.378 AC: 3732 AN: 9884

Middle Eastern (MID) AF: 0.409 AC: 104 AN: 254

European-Non Finnish (NFE) AF: 0.418 AC: 26714 AN: 63984

Other (OTH) AF: 0.508 AC: 921 AN: 1812

Alfa AF: 0.477 Hom.: 2524

Asia WGS AF: 0.517 AC: 1672 AN: 3236

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.47
DANN	Benign	0.36
PhyloP100		-1.9
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: rs438781; hg19: chr1-196796240; COSMIC: COSV57626532; COSMIC: COSV57626532;