rs60935272

Variant names:

• chr6-170299772-G-A
• rs60935272
• NM_001286380.2:c.48+4319G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-170299772-G-A
• chr6-170299772-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001286380.2(FAM120B):​c.48+4319G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00515 in 152,294 control chromosomes in the GnomAD database, including 8 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 0.0052 (8 hom., cov: 33)
• Consequence: FAM120B NM_001286380.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• 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=-0.84).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00515 (785/152294) while in subpopulation AFR AF = 0.0181 (750/41548). AF 95% confidence interval is 0.017. There are 8 homozygotes in GnomAd4. There are 359 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286380.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM120B	NM_001286380.2		c.48+4319G>A		intron	N/A	NP_001273309.1
	FAM120B	NM_001286379.2		c.15+8700G>A		intron	N/A	NP_001273308.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM120B	ENST00000537664.5	TSL:2	c.48+4319G>A		intron	N/A	ENSP00000440125.1
	FAM120B	ENST00000630384.2	TSL:2	c.15+8700G>A		intron	N/A	ENSP00000485745.1
	DLL1	ENST00000630500.1	TSL:4	c.-347+6754C>T		intron	N/A	ENSP00000486351.1

Frequencies

GnomAD3 genomes AF: 0.00515 AC: 783 AN: 152176 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

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

GnomAD4 genome AF: 0.00515 AC: 785 AN: 152294 Hom.: 8 Cov.: 33 AF XY: 0.00482 AC XY: 359 AN XY: 74468

African (AFR) AF: 0.0181 AC: 750 AN: 41548

American (AMR) AF: 0.00189 AC: 29 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00513 Hom.: 0

Bravo AF: 0.00566

Asia WGS AF: 0.00144 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.51
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs60935272; hg19: chr6-170608860;