1-196791287-A-G

Position:

• chr1-196791287-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021023.6(CFHR3):​c.796+1060A>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 135,238 control chromosomes in the GnomAD database, including 10,747 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (10747 hom., cov: 24)
• Consequence: CFHR3 NM_021023.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• 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	Protein	UniProt
CFHR3	NM_021023.6	c.796+1060A>G		intron_variant		ENST00000367425.9	NP_066303.2
CFHR3	NM_001166624.2	c.613+1060A>G		intron_variant			NP_001160096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFHR3	ENST00000367425.9	c.796+1060A>G		intron_variant		1	NM_021023.6	ENSP00000356395	P1
CFHR3	ENST00000391985.7	c.613+1060A>G		intron_variant		2		ENSP00000375845
CFHR3	ENST00000367427.7	c.*297+1060A>G		intron_variant, NMD_transcript_variant		5		ENSP00000356397
CFHR3	ENST00000461558.2	n.468+1060A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 37935 AN: 135108 Hom.: 10733 Cov.: 24

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.281 AC: 37966 AN: 135238 Hom.: 10747 Cov.: 24 AF XY: 0.279 AC XY: 18356 AN XY: 65812

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.263

Alfa AF: 0.262 Hom.: 1120

Asia WGS AF: 0.300 AC: 977 AN: 3256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.32

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: rs426736; hg19: chr1-196760417;