rs77087564

chr6-170295998-G-Achr6-170295998-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.974

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]

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM120B	NM_001286379.2	c.15+4926G>A		intron_variant
FAM120B	NM_001286380.2	c.48+545G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM120B	ENST00000537664.5	c.48+545G>A		intron_variant		2		A2
FAM120B	ENST00000630384.2	c.15+4926G>A		intron_variant		2		A2
DLL1	ENST00000630500.1	c.-346-5513C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17020 AN: 152006 Hom.: 1276 Cov.: 33

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.: 33 AF XY: 0.109 AC XY: 8137 AN XY: 74352

Gnomad4 AFR AF: 0.0349

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0639

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.127

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	6.3
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77087564; hg19: chr6-170605086;