chr20-20228340-G-A

Variant names:

• chr20-20228340-G-A
• rs34744783
• NM_015585.4:c.2024G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015585.4(CFAP61):​c.2024G>A​(p.Ser675Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000565 in 1,611,994 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0029 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (4 hom.)
• Consequence: CFAP61 NM_015585.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 2 publications found

Genes affected

CFAP61 (HGNC:15872): (cilia and flagella associated protein 61) Predicted to be involved in cilium movement and cilium organization. Predicted to be located in axoneme and motile cilium. Predicted to colocalize with radial spoke stalk. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.00456813).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00292 (444/152306) while in subpopulation AFR AF = 0.0101 (419/41566). AF 95% confidence interval is 0.00928. There are 3 homozygotes in GnomAd4. There are 225 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015585.4. 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
	CFAP61	NM_015585.4	MANE Select	c.2024G>A	p.Ser675Asn	missense	Exon 18 of 27	NP_056400.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP61	ENST00000245957.10	TSL:1 MANE Select	c.2024G>A	p.Ser675Asn	missense	Exon 18 of 27	ENSP00000245957.5	Q8NHU2-1
	CFAP61	ENST00000377293.5	TSL:1	c.92G>A	p.Ser31Asn	missense	Exon 2 of 6	ENSP00000366508.1	Q8NHU2-5
	CFAP61	ENST00000389656.4	TSL:1	c.92G>A	p.Ser31Asn	missense	Exon 1 of 5	ENSP00000374307.3	Q8NHU2-5

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 441 AN: 152188 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000760 AC: 191 AN: 251398 AF XY: 0.000648

Gnomad AFR exome AF: 0.0101

Gnomad AMR exome AF: 0.000694

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000320 AC: 467 AN: 1459688 Hom.: 4 Cov.: 29 AF XY: 0.000293 AC XY: 213 AN XY: 725970

African (AFR) AF: 0.0108 AC: 361 AN: 33460

American (AMR) AF: 0.000604 AC: 27 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5760

European-Non Finnish (NFE) AF: 0.00000901 AC: 10 AN: 1110330

Other (OTH) AF: 0.000945 AC: 57 AN: 60316

GnomAD4 genome AF: 0.00292 AC: 444 AN: 152306 Hom.: 3 Cov.: 33 AF XY: 0.00302 AC XY: 225 AN XY: 74470

African (AFR) AF: 0.0101 AC: 419 AN: 41566

American (AMR) AF: 0.00118 AC: 18 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00102 Hom.: 2

Bravo AF: 0.00292

ESP6500AA AF: 0.00817 AC: 36

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000799 AC: 97

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.011
DANN	Benign	0.38
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.21
PROVEAN	Benign	0.14	N
REVEL	Benign	0.060
Sift	Benign	0.28	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.059
MVP		0.15
MPC		0.10
ClinPred		0.017	T
GERP RS		-12
PromoterAI		0.030	Neutral
Varity_R		0.039
gMVP		0.40
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34744783; hg19: chr20-20208984;