6-170297621-G-T

Position:

• chr6-170297621-G-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+2168G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 145,724 control chromosomes in the GnomAD database, including 1,366 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 0.13 (1366 hom., cov: 32)
• Consequence: FAM120B NM_001286380.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.863

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM120B	NM_001286380.2	c.48+2168G>T		intron_variant			NP_001273309.1
FAM120B	NM_001286379.2	c.15+6549G>T		intron_variant			NP_001273308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM120B	ENST00000537664.5	c.48+2168G>T		intron_variant		2		ENSP00000440125.1
FAM120B	ENST00000630384.2	c.15+6549G>T		intron_variant		2		ENSP00000485745.1
DLL1	ENST00000630500.1	c.-346-7136C>A		intron_variant		4		ENSP00000486351.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 18338 AN: 145598 Hom.: 1364 Cov.: 32

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0719

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.126 AC: 18346 AN: 145724 Hom.: 1366 Cov.: 32 AF XY: 0.124 AC XY: 8761 AN XY: 70878

Gnomad4 AFR AF: 0.0616

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.0719

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.141

Alfa AF: 0.0821 Hom.: 138

Bravo AF: 0.125

Asia WGS AF: 0.209 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76301666; hg19: chr6-170606709; COSMIC: COSV73330098; COSMIC: COSV73330098;