rs11594962

Variant names:

• chr10-104156867-C-T
• rs11594962
• NM_025145.7:c.3541-4141G>A

Variant summary

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

The NM_025145.7(CFAP43):​c.3541-4141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0418 in 152,138 control chromosomes in the GnomAD database, including 193 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 0.042 (193 hom., cov: 32)
• Consequence: CFAP43 NM_025145.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 1 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

LOC751602 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP43	NM_025145.7	c.3541-4141G>A		intron_variant	Intron 27 of 37	ENST00000357060.8	NP_079421.5
LOC751602		n.104156867C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP43	ENST00000357060.8	c.3541-4141G>A		intron_variant	Intron 27 of 37	1	NM_025145.7	ENSP00000349568.3
CFAP43	ENST00000434629.5	c.1621-4141G>A		intron_variant	Intron 13 of 22	1		ENSP00000391364.1
CFAP43	ENST00000457071.5	c.85-4141G>A		intron_variant	Intron 1 of 11	2		ENSP00000394274.1
ENSG00000294028	ENST00000720641.1	n.109-5127C>T		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0419 AC: 6366 AN: 152020 Hom.: 193 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0349

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0663

Gnomad OTH AF: 0.0398

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

GnomAD4 genome AF: 0.0418 AC: 6364 AN: 152138 Hom.: 193 Cov.: 32 AF XY: 0.0404 AC XY: 3007 AN XY: 74366

African (AFR) AF: 0.0108 AC: 450 AN: 41534

American (AMR) AF: 0.0348 AC: 532 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5188

South Asian (SAS) AF: 0.00519 AC: 25 AN: 4818

European-Finnish (FIN) AF: 0.0607 AC: 641 AN: 10568

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0663 AC: 4506 AN: 67970

Other (OTH) AF: 0.0393 AC: 83 AN: 2110

Alfa AF: 0.0537 Hom.: 127

Bravo AF: 0.0393

Asia WGS AF: 0.00347 AC: 12 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.62
DANN	Benign	0.92
PhyloP100		-0.28
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: rs11594962; hg19: chr10-105916625;