rs441810

chr21-41326980-A-G

Variant summary

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

The NM_058186.4(FAM3B):c.163+3914A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,120 control chromosomes in the GnomAD database, including 13,127 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 0.35 (13127 hom., cov: 33)
• Consequence: FAM3B NM_058186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM3B	NM_058186.4	c.163+3914A>G		intron_variant		ENST00000357985.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM3B	ENST00000357985.7	c.163+3914A>G		intron_variant		1	NM_058186.4	P1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53707 AN: 152002 Hom.: 13069 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.354 AC: 53827 AN: 152120 Hom.: 13127 Cov.: 33 AF XY: 0.345 AC XY: 25648 AN XY: 74372

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.345

Alfa AF: 0.245 Hom.: 10191

Bravo AF: 0.380

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.20
Dann	Benign	0.35

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: rs441810; hg19: chr21-42698907;