1-109112908-C-A

Variant names:

• chr1-109112908-C-A
• rs569700390
• NM_001366200.3:c.45+725G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001366200.3(CFAP276):​c.45+725G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00619 in 131,770 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0062 (6 hom., cov: 32)
• Consequence: CFAP276 NM_001366200.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.705
• Publications: 1 publications found

Genes affected

CFAP276 (HGNC:32331): (cilia and flagella associated protein 276) Predicted to enable heme binding activity and heme transmembrane transporter activity. Predicted to be involved in heme export. Located in cytoplasm and cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CFAP276 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-109112908-C-A is Benign according to our data. Variant chr1-109112908-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2498411.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 815 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366200.3. 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
	CFAP276	NM_001366200.3		c.45+725G>T		intron	N/A	NP_001353129.1
	CFAP276	NM_001122961.3		c.45+725G>T		intron	N/A	NP_001116433.1	Q5T5A4-2
	CFAP276	NM_001366202.3		c.45+725G>T		intron	N/A	NP_001353131.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP276	ENST00000369949.8	TSL:2	c.45+725G>T		intron	N/A	ENSP00000358965.4	Q5T5A4-2
	CFAP276	ENST00000369942.2	TSL:5	n.203+725G>T		intron	N/A
	CFAP276	ENST00000462402.5	TSL:2	n.45+725G>T		intron	N/A	ENSP00000435090.1	E9PLX1

Frequencies

GnomAD3 genomes AF: 0.00619 AC: 815 AN: 131666 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00260

Gnomad AMI AF: 0.0547

Gnomad AMR AF: 0.00802

Gnomad ASJ AF: 0.0186

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00110

Gnomad FIN AF: 0.00120

Gnomad MID AF: 0.00662

Gnomad NFE AF: 0.00757

Gnomad OTH AF: 0.00536

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

GnomAD4 genome AF: 0.00619 AC: 815 AN: 131770 Hom.: 6 Cov.: 32 AF XY: 0.00566 AC XY: 365 AN XY: 64458

African (AFR) AF: 0.00259 AC: 72 AN: 27752

American (AMR) AF: 0.00801 AC: 108 AN: 13490

Ashkenazi Jewish (ASJ) AF: 0.0186 AC: 63 AN: 3386

East Asian (EAS) AF: 0.00 AC: 0 AN: 4220

South Asian (SAS) AF: 0.00110 AC: 5 AN: 4542

European-Finnish (FIN) AF: 0.00120 AC: 12 AN: 9996

Middle Eastern (MID) AF: 0.00709 AC: 2 AN: 282

European-Non Finnish (NFE) AF: 0.00758 AC: 495 AN: 65340

Other (OTH) AF: 0.00531 AC: 10 AN: 1884

Alfa AF: 0.00166 Hom.: 0

Bravo AF: 0.00579

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.56
PhyloP100		-0.70
PromoterAI		-0.073	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs569700390; hg19: chr1-109655530;