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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384237.2. 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
	FAM237B	NM_001384237.2	MANE Select	c.-50-19G>T		intron	N/A	NP_001371166.1	A0A1B0GVD1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FAM237B	ENST00000692316.1	MANE Select	c.-50-19G>T	intron	N/A	ENSP00000509180.1	A0A1B0GVD1
ENSG00000225498	ENST00000445784.1	TSL:1	n.369+325C>A	intron	N/A
FAM237B	ENST00000637645.2	TSL:5	c.-69G>T	5_prime_UTR	Exon 1 of 2	ENSP00000490466.1	A0A1B0GVD1

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 v4.9

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over