rs9459988

Variant names:

• chr6-170292460-T-G
• rs9459988
• NM_001286379.2:c.15+1388T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286379.2(FAM120B):​c.15+1388T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 151,848 control chromosomes in the GnomAD database, including 1,731 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 0.097 (1731 hom., cov: 32)
• Consequence: FAM120B NM_001286379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• Publications: 5 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: Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM120B	NM_001286379.2	c.15+1388T>G		intron_variant	Intron 1 of 10		NP_001273308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM120B	ENST00000630384.2	c.15+1388T>G		intron_variant	Intron 1 of 10	2		ENSP00000485745.1
DLL1	ENST00000630500.1	c.-346-1975A>C		intron_variant	Intron 1 of 2	4		ENSP00000486351.1

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14708 AN: 151730 Hom.: 1724 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0171

Gnomad EAS AF: 0.0219

Gnomad SAS AF: 0.0438

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0236

Gnomad OTH AF: 0.0797

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

GnomAD4 genome AF: 0.0971 AC: 14745 AN: 151848 Hom.: 1731 Cov.: 32 AF XY: 0.0943 AC XY: 7000 AN XY: 74224

African (AFR) AF: 0.281 AC: 11627 AN: 41382

American (AMR) AF: 0.0468 AC: 714 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 59 AN: 3460

East Asian (EAS) AF: 0.0218 AC: 112 AN: 5146

South Asian (SAS) AF: 0.0434 AC: 208 AN: 4794

European-Finnish (FIN) AF: 0.0195 AC: 206 AN: 10554

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0237 AC: 1607 AN: 67948

Other (OTH) AF: 0.0831 AC: 175 AN: 2106

Alfa AF: 0.0469 Hom.: 228

Bravo AF: 0.107

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.15
DANN	Benign	0.58
PhyloP100		-0.56
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: rs9459988; hg19: chr6-170601548;