6-170293341-T-C

Variant names:

• chr6-170293341-T-C
• rs17860704
• NM_001286379.2:c.15+2269T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001286379.2(FAM120B):​c.15+2269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 152,054 control chromosomes in the GnomAD database, including 1,363 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 0.074 (1363 hom., cov: 32)
• Consequence: FAM120B NM_001286379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.921
• Publications: 3 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, Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286379.2. 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_001286379.2		c.15+2269T>C		intron	N/A	NP_001273308.1	A0A0D9SEJ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM120B	ENST00000630384.2	TSL:2	c.15+2269T>C		intron	N/A	ENSP00000485745.1	A0A0D9SEJ5
	FAM120B	ENST00000966364.1		c.-181+2269T>C		intron	N/A	ENSP00000636423.1
	FAM120B	ENST00000915624.1		c.-181+2269T>C		intron	N/A	ENSP00000585683.1

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11243 AN: 151936 Hom.: 1361 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00584

Gnomad OTH AF: 0.0536

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

GnomAD4 genome AF: 0.0741 AC: 11264 AN: 152054 Hom.: 1363 Cov.: 32 AF XY: 0.0825 AC XY: 6128 AN XY: 74318

African (AFR) AF: 0.117 AC: 4856 AN: 41470

American (AMR) AF: 0.0673 AC: 1028 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.578 AC: 2975 AN: 5144

South Asian (SAS) AF: 0.164 AC: 787 AN: 4802

European-Finnish (FIN) AF: 0.100 AC: 1059 AN: 10572

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00584 AC: 397 AN: 68000

Other (OTH) AF: 0.0573 AC: 121 AN: 2110

Alfa AF: 0.0334 Hom.: 1168

Bravo AF: 0.0750

Asia WGS AF: 0.351 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17860704; hg19: chr6-170602429;