Genetic Variant NM_001164496.2:c.2934+2043C>A (chr3-113361102-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_001164496.2(CFAP44):c.2934+2043C>A variant causes a intron change. The variant allele was found at a frequency of 0.00104 in 207,766 control chromosomes in the GnomAD database, including 2 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 0.00092 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

CFAP44
NM_001164496.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.47

Publications

4 publications found

Variant links:

Genes affected

CFAP44 (HGNC:25631): (cilia and flagella associated protein 44) Enables peptidase activity. Involved in sperm axoneme assembly. Acts upstream of or within microtubule cytoskeleton organization. Predicted to be located in cytoplasm; cytoskeleton; and motile cilium. Implicated in spermatogenic failure 20. [provided by Alliance of Genome Resources, Apr 2022]

CFAP44 links:

RABGGTBP1 (HGNC:56479): (RABGGTB pseudogene 1)

RABGGTBP1 links:

SPICE1-CFAP44 (HGNC:58084):

SPICE1-CFAP44 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00092 (140/152104) while in subpopulation EAS AF = 0.0099 (51/5154). AF 95% confidence interval is 0.00773. There are 1 homozygotes in GnomAd4. There are 81 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164496.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CFAP44	NM_001164496.2	MANE Select	c.2934+2043C>A	intron	N/A	NP_001157968.1
SPICE1-CFAP44	NR_183045.1		n.5668+2043C>A	intron	N/A
SPICE1-CFAP44	NR_183046.1		n.5748+2043C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CFAP44	ENST00000393845.9	TSL:5 MANE Select	c.2934+2043C>A	intron	N/A	ENSP00000377428.2
RABGGTBP1	ENST00000462549.1	TSL:6	n.836G>T	non_coding_transcript_exon	Exon 1 of 1
CFAP44	ENST00000490481.1	TSL:5	n.165+2043C>A	intron	N/A	ENSP00000419269.1

Frequencies

GnomAD3 genomes

AF:

0.000928

AC:

141

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.0101

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00398

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000957

GnomAD4 exome

AF:

0.00138

AC:

AN:

55662

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

31930

show subpopulations

African (AFR)

AF:

0.00121

AC:

AN:

824

American (AMR)

AF:

0.00

AC:

AN:

2996

Ashkenazi Jewish (ASJ)

AF:

0.000888

AC:

AN:

1126

East Asian (EAS)

AF:

0.00433

AC:

AN:

1616

South Asian (SAS)

AF:

0.000381

AC:

AN:

7866

European-Finnish (FIN)

AF:

0.00384

AC:

AN:

7808

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.000882

AC:

AN:

30616

Other (OTH)

AF:

0.00311

AC:

AN:

2576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000920

AC:

140

AN:

152104

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41506

American (AMR)

AF:

0.000196

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3466

East Asian (EAS)

AF:

0.00990

AC:

AN:

5154

South Asian (SAS)

AF:

0.000622

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00398

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

67990

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00144

Hom.:

202

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.0

(source)

DANN

Benign

0.51

PhyloP100

5.5

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over