1-196828227-A-T

Variant names:

• chr1-196828227-A-T
• rs3201739
• NM_002113.3:c.588A>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002113.3(CFHR1):​c.588A>T​(p.Thr196Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000199 in 1,005,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T196T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 14)
  • Exomes 𝑓: 0.0000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFHR1 NM_002113.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-0.076 with no splicing effect.

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.588A>T	p.Thr196Thr	synonymous	Exon 4 of 6	NP_002104.2	Q03591
	CFHR1	NM_001379306.1		c.537A>T	p.Thr179Thr	synonymous	Exon 4 of 6	NP_001366235.1
	CFHR1	NM_001379307.1		c.426A>T	p.Thr142Thr	synonymous	Exon 4 of 6	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.588A>T	p.Thr196Thr	synonymous	Exon 4 of 6	ENSP00000314299.5	Q03591
	CFHR1	ENST00000887404.1		c.561A>T	p.Thr187Thr	synonymous	Exon 4 of 6	ENSP00000557463.1
	CFHR1	ENST00000887414.1		c.561A>T	p.Thr187Thr	synonymous	Exon 4 of 6	ENSP00000557473.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 91306 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000199 AC: 2 AN: 1005540 Hom.: 0 Cov.: 29 AF XY: 0.00000199 AC XY: 1 AN XY: 503114

African (AFR) AF: 0.00 AC: 0 AN: 15448

American (AMR) AF: 0.00 AC: 0 AN: 34490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17182

East Asian (EAS) AF: 0.00 AC: 0 AN: 30728

South Asian (SAS) AF: 0.00 AC: 0 AN: 58962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3640

European-Non Finnish (NFE) AF: 0.00000263 AC: 2 AN: 761380

Other (OTH) AF: 0.00 AC: 0 AN: 41432

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 91306 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 43990

African (AFR) AF: 0.00 AC: 0 AN: 17118

American (AMR) AF: 0.00 AC: 0 AN: 8738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2082

East Asian (EAS) AF: 0.00 AC: 0 AN: 3502

South Asian (SAS) AF: 0.00 AC: 0 AN: 2570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 204

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 47670

Other (OTH) AF: 0.00 AC: 0 AN: 1134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.9
DANN	Benign	0.72
PhyloP100		-0.076
Mutation Taster		=100/0	polymorphism

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: rs3201739; hg19: chr1-196797357;