dbSNP rs42611: FAM237B:c.-50-19G>T (chr7-90320746-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001384237.2(FAM237B):c.-50-19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,258 control chromosomes in the GnomAD database, including 19,920 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 0.50 ( 19901 hom., cov: 33)

Exomes 𝑓: 0.53 ( 19 hom. )

Consequence

FAM237B
NM_001384237.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.89

Publications

6 publications found

Variant links:

Genes affected

FAM237B (HGNC:53217): (family with sequence similarity 237 member B)

FAM237B links:

ENSG00000225498 (HGNC:):

ENSG00000225498 links:

CFAP69 (HGNC:26107): (cilia and flagella associated protein 69) Acts upstream of or within sperm axoneme assembly. Located in cytoplasm and sperm midpiece. Implicated in spermatogenic failure 24. [provided by Alliance of Genome Resources, Apr 2022]

CFAP69 Gene-Disease associations (from GenCC):

non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
spermatogenic failure 24
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CFAP69 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM237B	NM_001384237.2 link	c.-50-19G>T		intron_variant	Intron 1 of 2	ENST00000692316.1	NP_001371166.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
FAM237B	ENST00000692316.1 link	c.-50-19G>T	intron_variant	Intron 1 of 2		NM_001384237.2	ENSP00000509180.1
ENSG00000225498	ENST00000445784.1 link	n.369+325C>A	intron_variant	Intron 2 of 2	1
FAM237B	ENST00000637645.2 link	c.-69G>T	5_prime_UTR_variant	Exon 1 of 2	5		ENSP00000490466.1

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

75862

AN:

152020

Hom.:

19896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.514

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.600

Gnomad MID

AF:

0.599

Gnomad NFE

AF:

0.586

Gnomad OTH

AF:

0.493

GnomAD4 exome

AF:

0.525

AC:

AN:

120

Hom.:

Cov.:

AF XY:

0.511

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.545

AC:

AN:

110

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.499

AC:

75889

AN:

152138

Hom.:

19901

Cov.:

AF XY:

0.496

AC XY:

36883

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.393

AC:

16327

AN:

41508

American (AMR)

AF:

0.425

AC:

6500

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

1781

AN:

3466

East Asian (EAS)

AF:

0.211

AC:

1096

AN:

5184

South Asian (SAS)

AF:

0.467

AC:

2249

AN:

4818

European-Finnish (FIN)

AF:

0.600

AC:

6341

AN:

10566

Middle Eastern (MID)

AF:

0.572

AC:

167

AN:

292

European-Non Finnish (NFE)

AF:

0.586

AC:

39854

AN:

67996

Other (OTH)

AF:

0.497

AC:

1049

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1923

3847

5770

7694

9617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.554

Hom.:

3102

Bravo

AF:

0.479

Asia WGS

AF:

0.404

AC:

1410

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.040

(source)

DANN

Benign

0.75

PhyloP100

-3.9

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over