Genetic Variant FAM50B:c.*522G>C (chr6-3851311-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_012135.3(FAM50B):c.*522G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 171,118 control chromosomes in the GnomAD database, including 17,545 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 0.43 ( 14500 hom., cov: 33)

Exomes 𝑓: 0.55 ( 3045 hom. )

Consequence

FAM50B
NM_012135.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59

Publications

5 publications found

Variant links:

Genes affected

FAM50B (HGNC:18789): (family with sequence similarity 50 member B) This gene contains an intronless ORF that arose from ancestral retroposition. The encoded protein is related to a plant protein that plays a role in the circadian clock. This gene is adjacent to a differentially methylated region (DMR) and is imprinted and paternally expressed in many tissues. [provided by RefSeq, Nov 2015]

FAM50B links:

ENSG00000233068 (HGNC:):

ENSG00000233068 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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012135.3. 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
	FAM50B	NM_012135.3	MANE Select	c.*522G>C		3_prime_UTR	Exon 2 of 2	NP_036267.1	Q9Y247

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FAM50B	ENST00000648326.1	MANE Select	c.*522G>C	3_prime_UTR	Exon 2 of 2	ENSP00000496837.1	Q9Y247
FAM50B	ENST00000956903.1		c.*522G>C	splice_region	Exon 2 of 2	ENSP00000626962.1
FAM50B	ENST00000380274.2	TSL:6	c.*522G>C	3_prime_UTR	Exon 1 of 1	ENSP00000369627.1	Q9Y247

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64881

AN:

151932

Hom.:

14490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.607

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.452

Gnomad OTH

AF:

0.396

GnomAD4 exome

AF:

0.553

AC:

10550

AN:

19068

Hom.:

3045

Cov.:

AF XY:

0.548

AC XY:

5026

AN XY:

9174

show subpopulations

African (AFR)

AF:

0.409

AC:

AN:

American (AMR)

AF:

0.318

AC:

270

AN:

850

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

AN:

East Asian (EAS)

AF:

0.176

AC:

AN:

108

South Asian (SAS)

AF:

0.285

AC:

AN:

302

European-Finnish (FIN)

AF:

0.596

AC:

8687

AN:

14572

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.459

AC:

1354

AN:

2952

Other (OTH)

AF:

0.491

AC:

114

AN:

232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

185

370

555

740

925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.427

AC:

64936

AN:

152050

Hom.:

14500

Cov.:

AF XY:

0.429

AC XY:

31867

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.425

AC:

17624

AN:

41458

American (AMR)

AF:

0.344

AC:

5259

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1214

AN:

3472

East Asian (EAS)

AF:

0.188

AC:

975

AN:

5178

South Asian (SAS)

AF:

0.306

AC:

1471

AN:

4810

European-Finnish (FIN)

AF:

0.607

AC:

6405

AN:

10560

Middle Eastern (MID)

AF:

0.288

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.452

AC:

30700

AN:

67974

Other (OTH)

AF:

0.394

AC:

831

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1915

3830

5746

7661

9576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.353

Hom.:

1165

Bravo

AF:

0.406

Asia WGS

AF:

0.246

AC:

851

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.11

(source)

DANN

Benign

0.61

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over