chr6-170294897-G-C

Variant names:

• chr6-170294897-G-C
• rs9348307
• NM_001286379.2:c.15+3825G>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+3825G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,192 control chromosomes in the GnomAD database, including 1,338 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 0.11 (1338 hom., cov: 32)
• Consequence: FAM120B NM_001286379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM120B	NM_001286379.2	c.15+3825G>C		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+3825G>C		intron_variant	Intron 1 of 10	2		ENSP00000485745.1
DLL1	ENST00000630500.1	c.-346-4412C>G		intron_variant	Intron 1 of 2	4		ENSP00000486351.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17475 AN: 152074 Hom.: 1336 Cov.: 32

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0638

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.115 AC: 17482 AN: 152192 Hom.: 1338 Cov.: 32 AF XY: 0.113 AC XY: 8371 AN XY: 74402

African (AFR) AF: 0.0367 AC: 1523 AN: 41508

American (AMR) AF: 0.144 AC: 2210 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3472

East Asian (EAS) AF: 0.311 AC: 1610 AN: 5174

South Asian (SAS) AF: 0.170 AC: 818 AN: 4824

European-Finnish (FIN) AF: 0.0638 AC: 676 AN: 10596

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9703 AN: 68004

Other (OTH) AF: 0.132 AC: 278 AN: 2114

Alfa AF: 0.0640 Hom.: 63

Bravo AF: 0.118

Asia WGS AF: 0.214 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.78
PhyloP100		0.49
PromoterAI		-0.0020	Neutral
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: rs9348307; hg19: chr6-170603985;