rs4886636

Variant names:

• chr15-74903835-G-A
• rs4886636
• NM_020447.5:c.429+829C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020447.5(FAM219B):​c.429+829C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,864 control chromosomes in the GnomAD database, including 16,397 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 0.45 (16397 hom., cov: 30)
• Consequence: FAM219B NM_020447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 27 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

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.429+829C>T		intron	N/A	NP_065180.1
	FAM219B	NM_001321920.2		c.429+829C>T		intron	N/A	NP_001308849.1
	FAM219B	NM_001321921.2		c.429+829C>T		intron	N/A	NP_001308850.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM219B	ENST00000357635.10	TSL:1 MANE Select	c.429+829C>T		intron	N/A	ENSP00000350260.5
	FAM219B	ENST00000563119.5	TSL:1	c.429+829C>T		intron	N/A	ENSP00000454719.1
	FAM219B	ENST00000562698.5	TSL:1	c.429+829C>T		intron	N/A	ENSP00000454277.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68315 AN: 151748 Hom.: 16377 Cov.: 30

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.450 AC: 68389 AN: 151864 Hom.: 16397 Cov.: 30 AF XY: 0.440 AC XY: 32616 AN XY: 74186

African (AFR) AF: 0.340 AC: 14061 AN: 41392

American (AMR) AF: 0.517 AC: 7889 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3466

East Asian (EAS) AF: 0.229 AC: 1184 AN: 5168

South Asian (SAS) AF: 0.192 AC: 925 AN: 4814

European-Finnish (FIN) AF: 0.430 AC: 4519 AN: 10500

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36724 AN: 67950

Other (OTH) AF: 0.446 AC: 940 AN: 2108

Alfa AF: 0.512 Hom.: 83437

Bravo AF: 0.460

Asia WGS AF: 0.230 AC: 802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.14
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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: rs4886636; hg19: chr15-75196176; COSMIC: COSV61655769; COSMIC: COSV61655769;