6-170297621-G-T

Variant names:

• chr6-170297621-G-T
• rs76301666
• NM_001286380.2:c.48+2168G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

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, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, ClinGen
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

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+2168G>T		intron	N/A	NP_001273309.1	F5GY05
	FAM120B	NM_001286379.2		c.15+6549G>T		intron	N/A	NP_001273308.1	A0A0D9SEJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM120B	ENST00000537664.5	TSL:2	c.48+2168G>T		intron	N/A	ENSP00000440125.1	F5GY05
	FAM120B	ENST00000630384.2	TSL:2	c.15+6549G>T		intron	N/A	ENSP00000485745.1	A0A0D9SEJ5
	FAM120B	ENST00000966364.1		c.-181+6549G>T		intron	N/A	ENSP00000636423.1

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

African (AFR) AF: 0.0616 AC: 2455 AN: 39872

American (AMR) AF: 0.152 AC: 2245 AN: 14794

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 464 AN: 3402

East Asian (EAS) AF: 0.342 AC: 1588 AN: 4650

South Asian (SAS) AF: 0.178 AC: 751 AN: 4212

European-Finnish (FIN) AF: 0.0719 AC: 670 AN: 9314

Middle Eastern (MID) AF: 0.140 AC: 40 AN: 286

European-Non Finnish (NFE) AF: 0.146 AC: 9684 AN: 66250

Other (OTH) AF: 0.141 AC: 289 AN: 2054

Alfa AF: 0.0811 Hom.: 138

Bravo AF: 0.125

Asia WGS AF: 0.209 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		0.86
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs76301666;

hg19: chr6-170606709;

COSMIC: COSV73330098;

COSMIC: COSV73330098;