1-159886639-C-T

Variant names:

• chr1-159886639-C-T
• rs2501324
• NM_012337.3:c.639G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_012337.3(CFAP45):​c.639G>A​(p.Glu213Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00262 in 1,614,114 control chromosomes in the GnomAD database, including 100 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 0.014 (58 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (42 hom.)
• Consequence: CFAP45 NM_012337.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46
• Publications: 7 publications found

Genes affected

CFAP45 (HGNC:17229): (cilia and flagella associated protein 45) Enables AMP binding activity. Involved in establishment of left/right asymmetry and flagellated sperm motility. Located in 9+2 motile cilium; axoneme; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CFAP45 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 11, autosomal, with male infertility

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000272668 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2154/152284) while in subpopulation AFR AF = 0.0496 (2059/41542). AF 95% confidence interval is 0.0478. There are 58 homozygotes in GnomAd4. There are 1020 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012337.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP45	NM_012337.3	MANE Select	c.639G>A	p.Glu213Glu	synonymous	Exon 6 of 12	NP_036469.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP45	ENST00000368099.9	TSL:1 MANE Select	c.639G>A	p.Glu213Glu	synonymous	Exon 6 of 12	ENSP00000357079.4
	CFAP45	ENST00000426543.6	TSL:1	c.384G>A	p.Glu128Glu	synonymous	Exon 6 of 12	ENSP00000403044.2
	CFAP45	ENST00000479940.2	TSL:5	c.384G>A	p.Glu128Glu	synonymous	Exon 7 of 7	ENSP00000478944.1

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2144 AN: 152166 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00364 AC: 914 AN: 251438 AF XY: 0.00264

Gnomad AFR exome AF: 0.0493

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00142 AC: 2074 AN: 1461830 Hom.: 42 Cov.: 31 AF XY: 0.00123 AC XY: 897 AN XY: 727220

African (AFR) AF: 0.0488 AC: 1634 AN: 33472

American (AMR) AF: 0.00280 AC: 125 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5766

European-Non Finnish (NFE) AF: 0.0000468 AC: 52 AN: 1111966

Other (OTH) AF: 0.00366 AC: 221 AN: 60396

GnomAD4 genome AF: 0.0141 AC: 2154 AN: 152284 Hom.: 58 Cov.: 32 AF XY: 0.0137 AC XY: 1020 AN XY: 74472

African (AFR) AF: 0.0496 AC: 2059 AN: 41542

American (AMR) AF: 0.00419 AC: 64 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68024

Other (OTH) AF: 0.0109 AC: 23 AN: 2116

Alfa AF: 0.00671 Hom.: 56

Bravo AF: 0.0166

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	11
DANN	Benign	0.57
PhyloP100		4.5
Mutation Taster		=62/38	polymorphism

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: rs2501324; hg19: chr1-159856429;