15-74906786-C-T

Variant names:

• chr15-74906786-C-T
• rs1416706695
• NM_020447.5:c.15G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020447.5(FAM219B):​c.15G>A​(p.Glu5Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM219B NM_020447.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 0 publications found

Genes affected

FAM219B (HGNC:24695): (family with sequence similarity 219 member B)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-0.293 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020447.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM219B	NM_020447.5	MANE Select	c.15G>A	p.Glu5Glu	synonymous	Exon 1 of 5	NP_065180.1	Q5XKK7-1
	FAM219B	NM_001321920.2		c.15G>A	p.Glu5Glu	synonymous	Exon 1 of 6	NP_001308849.1	Q5XKK7-1
	FAM219B	NM_001321921.2		c.15G>A	p.Glu5Glu	synonymous	Exon 1 of 6	NP_001308850.1	Q5XKK7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM219B	ENST00000357635.10	TSL:1 MANE Select	c.15G>A	p.Glu5Glu	synonymous	Exon 1 of 5	ENSP00000350260.5	Q5XKK7-1
	FAM219B	ENST00000563119.5	TSL:1	c.15G>A	p.Glu5Glu	synonymous	Exon 1 of 6	ENSP00000454719.1	Q5XKK7-1
	FAM219B	ENST00000562698.5	TSL:1	c.15G>A	p.Glu5Glu	synonymous	Exon 1 of 5	ENSP00000454277.1	H3BM86

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1134892 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 540208

African (AFR) AF: 0.00 AC: 0 AN: 23066

American (AMR) AF: 0.00 AC: 0 AN: 8738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15222

East Asian (EAS) AF: 0.00 AC: 0 AN: 26674

South Asian (SAS) AF: 0.00 AC: 0 AN: 31444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3166

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 949972

Other (OTH) AF: 0.00 AC: 0 AN: 46138

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.1
DANN	Benign	0.90
PhyloP100		-0.29
PromoterAI		-0.11	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1416706695; hg19: chr15-75199127;