rs11073328

chr15-38472642-C-T

Variant summary

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

The NM_173611.4(FAM98B):c.532-863C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 151,952 control chromosomes in the GnomAD database, including 827 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 0.094 (827 hom., cov: 32)
• Consequence: FAM98B NM_173611.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.671

Genes affected

FAM98B (HGNC:26773): (family with sequence similarity 98 member B) Enables identical protein binding activity and protein methyltransferase activity. Involved in positive regulation of cell population proliferation; positive regulation of gene expression; and protein methylation. Located in cytoplasm and nucleoplasm. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM98B	NM_173611.4	c.532-863C>T		intron_variant		ENST00000397609.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM98B	ENST00000397609.6	c.532-863C>T		intron_variant		5	NM_173611.4	P1
FAM98B	ENST00000491535.5	c.532-863C>T		intron_variant		1
FAM98B	ENST00000559431.1	c.238-863C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14312 AN: 151832 Hom.: 824 Cov.: 32

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0989

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0988

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

GnomAD4 genome AF: 0.0943 AC: 14331 AN: 151952 Hom.: 827 Cov.: 32 AF XY: 0.0962 AC XY: 7138 AN XY: 74238

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0991

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.104

Alfa AF: 0.112 Hom.: 2249

Bravo AF: 0.0941

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.0
Dann	Benign	0.57

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: rs11073328; hg19: chr15-38764843;