chr18-50261232-C-T

Position:

• chr18-50261232-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_145020.5(CFAP53):​c.305G>A​(p.Arg102His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,461,570 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (8 hom., cov: 28)
  • Exomes 𝑓: 0.00067 (11 hom.)
• Consequence: CFAP53 NM_145020.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.46

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007839054).
• BP6: Variant 18-50261232-C-T is Benign according to our data. Variant chr18-50261232-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-50261232-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00662 (916/138446) while in subpopulation AFR AF= 0.0233 (849/36492). AF 95% confidence interval is 0.022. There are 8 homozygotes in gnomad4. There are 407 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP53	NM_145020.5	c.305G>A	p.Arg102His	missense_variant	3/8	ENST00000398545.5	NP_659457.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP53	ENST00000398545.5	c.305G>A	p.Arg102His	missense_variant	3/8	1	NM_145020.5	ENSP00000381553	P1

Frequencies

GnomAD3 genomes AF: 0.00656 AC: 908 AN: 138392 Hom.: 8 Cov.: 28

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00375

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000122

Gnomad OTH AF: 0.00597

GnomAD3 exomes AF: 0.00197 AC: 281 AN: 142736 Hom.: 4 AF XY: 0.00147 AC XY: 119 AN XY: 80892

Gnomad AFR exome AF: 0.0255

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.000180

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000115

Gnomad FIN exome AF: 0.0000725

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000667 AC: 883 AN: 1323124 Hom.: 11 Cov.: 36 AF XY: 0.000614 AC XY: 401 AN XY: 652692

Gnomad4 AFR exome AF: 0.0232

Gnomad4 AMR exome AF: 0.00167

Gnomad4 ASJ exome AF: 0.000462

Gnomad4 EAS exome AF: 0.0000590

Gnomad4 SAS exome AF: 0.000234

Gnomad4 FIN exome AF: 0.0000924

Gnomad4 NFE exome AF: 0.0000827

Gnomad4 OTH exome AF: 0.00170

GnomAD4 genome AF: 0.00662 AC: 916 AN: 138446 Hom.: 8 Cov.: 28 AF XY: 0.00614 AC XY: 407 AN XY: 66258

Gnomad4 AFR AF: 0.0233

Gnomad4 AMR AF: 0.00367

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000122

Gnomad4 OTH AF: 0.00591

Alfa AF: 0.000793 Hom.: 3

ESP6500AA AF: 0.0179 AC: 64

ESP6500EA AF: 0.000492 AC: 4

ExAC AF: 0.00225 AC: 271

Asia WGS AF: 0.00173 AC: 6 AN: 3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Heterotaxy, visceral, 6, autosomal Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 26, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.13
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.47
MVP		0.49
MPC		0.42
ClinPred		0.037	T
GERP RS		6.1
Varity_R		0.19
gMVP		0.057

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs76722120; hg19: chr18-47787602;