rs4886636

Positions:

• chr15-74903835-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000357635.10(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 ENST00000357635.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM219B	NM_020447.5	c.429+829C>T		intron_variant		ENST00000357635.10	NP_065180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM219B	ENST00000357635.10	c.429+829C>T		intron_variant		1	NM_020447.5	ENSP00000350260	P1

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

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.446

Alfa AF: 0.516 Hom.: 39576

Bravo AF: 0.460

Asia WGS AF: 0.230 AC: 802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.14

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

Publications

LitVar

Other links and lift over

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