rs9366198

Positions:

• chr6-170299862-C-G
• chr6-170299862-C-T

Variant summary

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

The NM_001286380.2(FAM120B):​c.48+4409C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,224 control chromosomes in the GnomAD database, including 4,256 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 0.23 (4256 hom., cov: 33)
• Consequence: FAM120B NM_001286380.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM120B	NM_001286379.2	c.15+8790C>G		intron_variant			NP_001273308.1
FAM120B	NM_001286380.2	c.48+4409C>G		intron_variant			NP_001273309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM120B	ENST00000537664.5	c.48+4409C>G		intron_variant		2		ENSP00000440125	A2
FAM120B	ENST00000630384.2	c.15+8790C>G		intron_variant		2		ENSP00000485745	A2
DLL1	ENST00000630500.1	c.-347+6664G>C		intron_variant		4		ENSP00000486351

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34819 AN: 152106 Hom.: 4242 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.229 AC: 34863 AN: 152224 Hom.: 4256 Cov.: 33 AF XY: 0.222 AC XY: 16531 AN XY: 74436

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.226

Alfa AF: 0.218 Hom.: 446

Bravo AF: 0.238

Asia WGS AF: 0.314 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.090
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9366198; hg19: chr6-170608950;