1-196779546-A-G

Position:

• chr1-196779546-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021023.6(CFHR3):​c.253+190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 135,410 control chromosomes in the GnomAD database, including 10,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (10821 hom., cov: 24)
• Consequence: CFHR3 NM_021023.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.221

Genes affected

CFHR3 (HGNC:16980): (complement factor H related 3) The protein encoded by this gene is a secreted protein, which belongs to the complement factor H-related protein family. It binds to heparin, and may be involved in complement regulation. Mutations in this gene are associated with decreased risk of age-related macular degeneration, and with an increased risk of atypical hemolytic-uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-196779546-A-G is Benign according to our data. Variant chr1-196779546-A-G is described in ClinVar as [Benign]. Clinvar id is 1222856.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFHR3	NM_021023.6	c.253+190A>G		intron_variant		ENST00000367425.9
CFHR3	NM_001166624.2	c.253+190A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFHR3	ENST00000367425.9	c.253+190A>G		intron_variant		1	NM_021023.6	P1
CFHR3	ENST00000471440.6	c.253+190A>G		intron_variant		1
CFHR3	ENST00000391985.7	c.253+190A>G		intron_variant		2
CFHR3	ENST00000367427.7	c.253+190A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.282 AC: 38088 AN: 135292 Hom.: 10810 Cov.: 24

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.281 AC: 38113 AN: 135410 Hom.: 10821 Cov.: 24 AF XY: 0.280 AC XY: 18430 AN XY: 65896

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.272

Alfa AF: 0.262 Hom.: 1131

Asia WGS AF: 0.300 AC: 973 AN: 3248

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs620015; hg19: chr1-196748676;