NM_001286380.2:c.48+517G>A

Variant names:

• chr6-170295970-G-A
• rs12200136
• NM_001286380.2:c.48+517G>A

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+517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 152,004 control chromosomes in the GnomAD database, including 249 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 0.049 (249 hom., cov: 33)
• Consequence: FAM120B NM_001286380.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• 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: 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM120B	NM_001286380.2	c.48+517G>A		intron_variant	Intron 1 of 10		NP_001273309.1
FAM120B	NM_001286379.2	c.15+4898G>A		intron_variant	Intron 1 of 10		NP_001273308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM120B	ENST00000537664.5	c.48+517G>A		intron_variant	Intron 1 of 10	2		ENSP00000440125.1
FAM120B	ENST00000630384.2	c.15+4898G>A		intron_variant	Intron 1 of 10	2		ENSP00000485745.1
DLL1	ENST00000630500.1	c.-346-5485C>T		intron_variant	Intron 1 of 2	4		ENSP00000486351.1

Frequencies

GnomAD3 genomes AF: 0.0486 AC: 7389 AN: 151890 Hom.: 249 Cov.: 33

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0439

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

GnomAD4 genome AF: 0.0486 AC: 7390 AN: 152004 Hom.: 249 Cov.: 33 AF XY: 0.0507 AC XY: 3768 AN XY: 74284

African (AFR) AF: 0.0106 AC: 439 AN: 41516

American (AMR) AF: 0.0386 AC: 590 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3468

East Asian (EAS) AF: 0.000393 AC: 2 AN: 5092

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4820

European-Finnish (FIN) AF: 0.124 AC: 1315 AN: 10586

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0657 AC: 4462 AN: 67914

Other (OTH) AF: 0.0435 AC: 92 AN: 2116

Alfa AF: 0.0247 Hom.: 14

Bravo AF: 0.0425

Asia WGS AF: 0.0100 AC: 36 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.1
DANN	Benign	0.96
PhyloP100		-2.0
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: rs12200136; hg19: chr6-170605058;