dbSNP rs77087564: FAM120B:c.48+545G>A (chr6-170295998-G-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_001286380.2(FAM120B):c.48+545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,118 control chromosomes in the GnomAD database, including 1,278 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 0.11 ( 1278 hom., cov: 33)

Consequence

FAM120B
NM_001286380.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.974

Publications

0 publications found

Variant links:

Genes affected

FAM120B (HGNC:21109): (family with sequence similarity 120 member B) Predicted to be involved in fat cell differentiation and peroxisome proliferator activated receptor signaling pathway. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM120B links:

DLL1 (HGNC:2908): (delta like canonical Notch ligand 1) DLL1 is a human homolog of the Notch Delta ligand and is a member of the delta/serrate/jagged family. It plays a role in mediating cell fate decisions during hematopoiesis. It may play a role in cell-to-cell communication. [provided by RefSeq, Jul 2008]

DLL1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DLL1 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=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286380.2. 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
	FAM120B	NM_001286380.2		c.48+545G>A		intron	N/A	NP_001273309.1	F5GY05
	FAM120B	NM_001286379.2		c.15+4926G>A		intron	N/A	NP_001273308.1	A0A0D9SEJ5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FAM120B	ENST00000537664.5	TSL:2	c.48+545G>A	intron	N/A	ENSP00000440125.1	F5GY05
FAM120B	ENST00000630384.2	TSL:2	c.15+4926G>A	intron	N/A	ENSP00000485745.1	A0A0D9SEJ5
FAM120B	ENST00000966364.1		c.-181+4926G>A	intron	N/A	ENSP00000636423.1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17020

AN:

152006

Hom.:

1276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.0639

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.128

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.112

AC:

17021

AN:

152118

Hom.:

1278

Cov.:

AF XY:

0.109

AC XY:

8137

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0349

AC:

1452

AN:

41554

American (AMR)

AF:

0.125

AC:

1909

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

463

AN:

3472

East Asian (EAS)

AF:

0.310

AC:

1574

AN:

5076

South Asian (SAS)

AF:

0.168

AC:

809

AN:

4822

European-Finnish (FIN)

AF:

0.0639

AC:

678

AN:

10610

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9667

AN:

67958

Other (OTH)

AF:

0.127

AC:

269

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

738

1476

2213

2951

3689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<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:

0.114

Hom.:

130

Bravo

AF:

0.114

Asia WGS

AF:

0.210

AC:

730

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.3

(source)

DANN

Benign

0.75

PhyloP100

-0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over