rs2738820

Variant names:

• chr6-170292171-C-A
• rs2738820
• NM_001286379.2:c.15+1099C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-170292171-C-A
• chr6-170292171-C-T

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+1099C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,106 control chromosomes in the GnomAD database, including 20,539 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 0.50 (20539 hom., cov: 33)
• Consequence: FAM120B NM_001286379.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.783
• Publications: 7 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=-0.63).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM120B	NM_001286379.2	c.15+1099C>A		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+1099C>A		intron_variant	Intron 1 of 10	2		ENSP00000485745.1
DLL1	ENST00000630500.1	c.-346-1686G>T		intron_variant	Intron 1 of 2	4		ENSP00000486351.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75742 AN: 151988 Hom.: 20539 Cov.: 33

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.00867

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.498 AC: 75756 AN: 152106 Hom.: 20539 Cov.: 33 AF XY: 0.493 AC XY: 36659 AN XY: 74362

African (AFR) AF: 0.336 AC: 13957 AN: 41484

American (AMR) AF: 0.543 AC: 8303 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2037 AN: 3466

East Asian (EAS) AF: 0.00907 AC: 47 AN: 5180

South Asian (SAS) AF: 0.443 AC: 2136 AN: 4824

European-Finnish (FIN) AF: 0.569 AC: 6029 AN: 10594

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41467 AN: 67942

Other (OTH) AF: 0.508 AC: 1075 AN: 2116

Alfa AF: 0.576 Hom.: 15064

Bravo AF: 0.487

Asia WGS AF: 0.222 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		0.78
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: rs2738820; hg19: chr6-170601259;