rs515910

Variant names:

• chr10-104206646-A-G
• rs515910
• NM_025145.7:c.896-616T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025145.7(CFAP43):​c.896-616T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,032 control chromosomes in the GnomAD database, including 17,787 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 0.47 (17787 hom., cov: 31)
• Consequence: CFAP43 NM_025145.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.790
• Publications: 19 publications found

Genes affected

CFAP43 (HGNC:26684): (cilia and flagella associated protein 43) This gene encodes a member of the cilia- and flagella-associated protein family. [provided by RefSeq, Sep 2016]

CFAP43 Gene-Disease associations (from GenCC):

• spermatogenic failure 19

  Inheritance: AR Classification: DEFINITIVE, LIMITED Submitted by: ClinGen, Ambry Genetics
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• normal pressure hydrocephalus

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP43	NM_025145.7	c.896-616T>C		intron_variant	Intron 6 of 37	ENST00000357060.8	NP_079421.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP43	ENST00000357060.8	c.896-616T>C		intron_variant	Intron 6 of 37	1	NM_025145.7	ENSP00000349568.3
CFAP43	ENST00000278064.7	c.896-613T>C		intron_variant	Intron 6 of 21	1		ENSP00000278064.3
CFAP43	ENST00000369720.6	c.896-613T>C		intron_variant	Intron 6 of 10	1		ENSP00000358734.2
CFAP43	ENST00000369719.2	c.896-613T>C		intron_variant	Intron 6 of 7	2		ENSP00000358733.2

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71481 AN: 151914 Hom.: 17743 Cov.: 31

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.471 AC: 71579 AN: 152032 Hom.: 17787 Cov.: 31 AF XY: 0.470 AC XY: 34939 AN XY: 74304

African (AFR) AF: 0.652 AC: 27013 AN: 41458

American (AMR) AF: 0.412 AC: 6299 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1437 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1987 AN: 5154

South Asian (SAS) AF: 0.515 AC: 2487 AN: 4828

European-Finnish (FIN) AF: 0.365 AC: 3862 AN: 10578

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27087 AN: 67950

Other (OTH) AF: 0.455 AC: 958 AN: 2104

Alfa AF: 0.433 Hom.: 28709

Bravo AF: 0.478

Asia WGS AF: 0.508 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.81
DANN	Benign	0.77
PhyloP100		-0.79
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: rs515910; hg19: chr10-105966404;