15-74906746-G-T

Variant names:

• chr15-74906746-G-T
• rs1442147612
• NM_020447.5:c.55C>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.55C>A​(p.Arg19Arg) 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: 0.640
• 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=-0.71).
• BP7: Synonymous conserved (PhyloP=0.64 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.55C>A	p.Arg19Arg	synonymous	Exon 1 of 5	NP_065180.1	Q5XKK7-1
	FAM219B	NM_001321920.2		c.55C>A	p.Arg19Arg	synonymous	Exon 1 of 6	NP_001308849.1	Q5XKK7-1
	FAM219B	NM_001321921.2		c.55C>A	p.Arg19Arg	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.55C>A	p.Arg19Arg	synonymous	Exon 1 of 5	ENSP00000350260.5	Q5XKK7-1
	FAM219B	ENST00000563119.5	TSL:1	c.55C>A	p.Arg19Arg	synonymous	Exon 1 of 6	ENSP00000454719.1	Q5XKK7-1
	FAM219B	ENST00000562698.5	TSL:1	c.55C>A	p.Arg19Arg	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: 1173494 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 562528

African (AFR) AF: 0.00 AC: 0 AN: 23532

American (AMR) AF: 0.00 AC: 0 AN: 10004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15772

East Asian (EAS) AF: 0.00 AC: 0 AN: 27368

South Asian (SAS) AF: 0.00 AC: 0 AN: 39478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 967922

Other (OTH) AF: 0.00 AC: 0 AN: 47492

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.2
DANN	Benign	0.65
PhyloP100		0.64
PromoterAI		0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1442147612; hg19: chr15-75199087;