rs6517664

Positions:

• chr21-41333056-C-T

Variant summary

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

The NM_058186.4(FAM3B):​c.164-5322C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 147,896 control chromosomes in the GnomAD database, including 725 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 0.083 (725 hom., cov: 31)
• Consequence: FAM3B NM_058186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

Genes affected

FAM3B (HGNC:1253): (FAM3 metabolism regulating signaling molecule B) Involved in insulin secretion. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

FAM3B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM3B	NM_058186.4	c.164-5322C>T		intron_variant		ENST00000357985.7	NP_478066.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM3B	ENST00000357985.7	c.164-5322C>T		intron_variant		1	NM_058186.4	ENSP00000350673.2
FAM3B	ENST00000398652.7	c.281-5322C>T		intron_variant		1		ENSP00000381646.3

Frequencies

GnomAD3 genomes AF: 0.0826 AC: 12204 AN: 147834 Hom.: 722 Cov.: 31

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0609

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.0789

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0749

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

GnomAD4 genome AF: 0.0827 AC: 12228 AN: 147896 Hom.: 725 Cov.: 31 AF XY: 0.0809 AC XY: 5815 AN XY: 71884

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0608

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.0202

Gnomad4 FIN AF: 0.0335

Gnomad4 NFE AF: 0.0564

Gnomad4 OTH AF: 0.0744

Alfa AF: 0.0633 Hom.: 381

Bravo AF: 0.0871

Asia WGS AF: 0.0230 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.40
DANN	Benign	0.84

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: rs6517664; hg19: chr21-42704983;