chr18-50250809-T-C

Variant names:

• chr18-50250809-T-C
• rs368815693
• NM_145020.5:c.945A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_145020.5(CFAP53):​c.945A>G​(p.Gln315Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,614,222 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: CFAP53 NM_145020.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.165
• Publications: 0 publications found

Genes affected

CFAP53 (HGNC:26530): (cilia and flagella associated protein 53) This gene belongs to the CFAP53 family. It was found to be differentially expressed by the ciliated cells of frog epidermis and in skin fibroblasts from human. Mutations in this gene are associated with visceral heterotaxy-6, which implicates this gene in determination of left-right asymmetric patterning. [provided by RefSeq, Aug 2015]

CFAP53 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 6, autosomal

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-50250809-T-C is Benign according to our data. Variant chr18-50250809-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.165 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000263 (40/152344) while in subpopulation EAS AF = 0.00482 (25/5188). AF 95% confidence interval is 0.00335. There are 1 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145020.5. 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
	CFAP53	NM_145020.5	MANE Select	c.945A>G	p.Gln315Gln	synonymous	Exon 5 of 8	NP_659457.2	Q96M91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP53	ENST00000398545.5	TSL:1 MANE Select	c.945A>G	p.Gln315Gln	synonymous	Exon 5 of 8	ENSP00000381553.3	Q96M91
	CFAP53	ENST00000880606.1		c.933A>G	p.Gln311Gln	synonymous	Exon 5 of 8	ENSP00000550665.1

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152226 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000353 AC: 88 AN: 249550 AF XY: 0.000332

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00334

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000110 AC: 161 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.000114 AC XY: 83 AN XY: 727238

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00154 AC: 61 AN: 39698

South Asian (SAS) AF: 0.000475 AC: 41 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112006

Other (OTH) AF: 0.000844 AC: 51 AN: 60394

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152344 Hom.: 1 Cov.: 33 AF XY: 0.000322 AC XY: 24 AN XY: 74504

African (AFR) AF: 0.0000962 AC: 4 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15308

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

East Asian (EAS) AF: 0.00482 AC: 25 AN: 5188

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.0000854 Hom.: 0

Bravo AF: 0.000151

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Heterotaxy, visceral, 6, autosomal (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.48
PhyloP100		0.17
Mutation Taster		=100/0	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: rs368815693; hg19: chr18-47777179; COSMIC: COSV68352000;